Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are...Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are not yet fully understood.Cytochrome P450 monooxygenases(CYP450s)serve biosynthesis and metabolic detoxification functions in plants,but there is limited information about their role in the response induced by RSB.This study demonstrated that CYT02 belongs to the CYP73A100 subfamily and is a typical member of the CYP450s.Overexpression(OE)in rice of the cytochrome P450 monooxygenase cyt02 conferred increased resistance to RSB and increased vegetative tillering.Cyt02 may increase RSB resistance by regulating plant hormone synthesis,regulate reactive oxygen species(ROS)by coordinating the activity of antioxidant enzymes,and initiate phytoalexin synthesis in response to fungal infection.These research findings have laid a foundation for a deeper understanding of the function of cyt02 and offered a potential target gene for breeding rice varieties resistant to sheath blight.展开更多
BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effec...BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effective treatment options remain limited.AIM To evaluate the therapeutic impact of Shenzhuo formulation(SZF)on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.METHODS We established a DN mouse model through a high-fat diet combined with streptozotocin(STZ)injection,followed by SZF treatment.We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques.Additionally,based on transcriptomic and non-targeted metabolomic findings,we further assessed SZF’s influence on the expression of factors related to the cytochrome P450(CYP450)-mediated arachidonic acid(AA)metabolism pathway,as well as its effects on inflammation and oxidative stress.RESULTS SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice.Pathological analysis revealed that SZF treatment improved renal tissue damage,reduced fibrosis,and diminished glycogen deposition.Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes,including Cyp2j13,Cyp2b9,Pla2 g2e/Cyp4a12a,Cyp4a32,Cyp2e1,and Cyp4a14.Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway,including 5,6-EET,14,15-EET,phosphatidylcholine,and 20-HETE.Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue,as well as CYP2J and CYP2B proteins.Additionally,SZF significantly reduced the expression of inflammatory factors in renal tissue,enhanced antioxidant enzyme activity,and alleviated oxidative stress.CONCLUSION SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism,leading to improved renal function and improved pathological state in DN mice.展开更多
The cytochrome P4503A(CYP3A)gene family’s role in early progression of gastric cancer was comprehensively investigated.Its potential as a therapeutic target was evaluated.Upon literature review,aberrant expression of...The cytochrome P4503A(CYP3A)gene family’s role in early progression of gastric cancer was comprehensively investigated.Its potential as a therapeutic target was evaluated.Upon literature review,aberrant expression of the CYP3A gene family has a strong correlation with gastric cancer onset,although the precise underlying mechanisms remain unclear.To assess its potential as a biomarker for early diagnosis and a therapeutic target,we have provided a comprehensive review of the regulatory mechanisms governing CYP3A gene family expression in gastric cancer,as well as its relation with early tumor progression and the tumor microenvironment.The CYP3A gene family is crucial in the proliferation,migration,and invasion of gastric cancer cells and promotes cancer progression by modulating inflammatory responses and oxidative stress within the tumor microenvironment.Furthermore,genetic polymorphisms in CYP3A enzymes highlight its potential value in personalized medicine.Based on these findings,this paper explores the feasibility of developing inhibitors and activators targeting CYP3A enzymes and discusses potential applications in gene therapy.This research provides crucial theoretical support for the CYP3A gene family as an early diagnostic marker and therapeutic target for gastric cancer.In the future,multi-omics studies and large-scale clinical trials will be essential to advance clinical translation of these findings.展开更多
The tobacco whitefly,Bemisia tabaci,is a notorious pest affecting various crops globally,and it exhibits high levels of resistance to various insecticides.Afidopyropen is a recently commercialized pyropene insecticide...The tobacco whitefly,Bemisia tabaci,is a notorious pest affecting various crops globally,and it exhibits high levels of resistance to various insecticides.Afidopyropen is a recently commercialized pyropene insecticide for B.tabaci control with high selectivity and a novel mode of action.We previously identified a high level of afidopyropen resistance in a field-collected population after selection in the lab,and named it the HD-Afi strain.In the present study,minimal cross-resistance in the HD-Afi strain was found between afidopyropen and other common chemical agents.However,the P450 enzyme activity in HD-Afi was 2.18 times the level in susceptible strain HD-S.Expression analysis revealed that two of 12 candidate P450 genes,namely CYP6DW3 and CYP4C64,were significantly up-regulated in HD-Afi.Silencing CYP6DW3 and CYP4C64 by RNA interference(RNAi)substantially increased the susceptibility of whitefly adults,confirming their involvement in afidopyropen resistance.Homology modeling and molecular docking analyses demonstrated stable binding of afidopyropen to CYP6DW3 and CYP4C64,with binding free energies of–6.87 and–6.11 kcal mol^(-1),respectively.The findings of this study suggest that the induction of CYP6DW3 and CYP4C64 facilitates afidopyropen detoxification,contributing to the development of resistance in B.tabaci.展开更多
Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of ...Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework.展开更多
BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to...BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.展开更多
Thirty-three mutations and four different haplotypes were found when cytochrome b（Cytb） gene partial sequences of 12 gayals were analyzed. Together with sequences of Bos indicus, Bos taurus, Bos grunniens, and Bos g...Thirty-three mutations and four different haplotypes were found when cytochrome b（Cytb） gene partial sequences of 12 gayals were analyzed. Together with sequences of Bos indicus, Bos taurus, Bos grunniens, and Bos gaurus with Bubalus bubalis as the out group, the partial sequences of Cytb gene of gayals were aligned and base composition and nucleotide variation of Cytb gene were analyzed. The phylogenetic trees were constructed by the NJ method and the MP method respectively, both supporting almost the same topology. Gayal is an independent species of Bos from Bos indicus, Bos taurus, and Bos gaurus. The results also indicate that a great proportion of gayal bloodline was invaded by other species, and the protection of gayal is facing a formidable situation.展开更多
[Objective] The aim was to explore the phylogenetic relationships among four subspecies of the genus Locusta.[Method] The sequences of three subunits of cytochrome oxidase of Locusta migratoria tibetensis and Locusta ...[Objective] The aim was to explore the phylogenetic relationships among four subspecies of the genus Locusta.[Method] The sequences of three subunits of cytochrome oxidase of Locusta migratoria tibetensis and Locusta migratoria manilensis were amplified and sequenced（COⅠ 1 539 bp,COⅡ 684 bp,CO Ⅲ 792 bp,with the total of 3 015 bp）.The corresponding sequenses of Locusta migratoria migratoria and Locusta migratoria migratorioides were obtained from GenBank and constructed a multiple alignment.Phylogenic trees of four subspecies of L.migratoria were constructed by Neighbor-Joining,Maximum-parsimony and Bayesian,respectively.[Result] The average content of A ＋ T in three subunits of four subspecies was 69.57%;the third site of codon showed the highest A ＋ T content,and the COⅠ had the highest A ＋ T content（87.6%）;The nucleotide substitution mainly occurred at the third site of codon,and the nucleotide replacement rate of CO Ⅱ was the highest.The second site of codon was conservative,so the replacement rate was in the range of 5.9%-15%.The start codon of COⅠ was CCG or ACG.Genetic distances among four subspecies were ranged from 0.001 to 0.076.The relationship between L.m.tibetensis and Locusta migratoria manilensis was the closest,followed by L.m.migratorioides and L.m.migratorioides,while the genetic distance between L.m.tibetensis and L.m.migratorioides was the largest.[Conclusion] The phylogenetic relationships among four subspecies of Locusta migratoria is L.m.tibetensis,L.m.manilensis,L.m.migratoria,L.m.migratorioides.展开更多
A lipid_depleted cytochrome b 6f (Cyt b 6f) preparation was obtained from spinach (Spinacia oleracea L.) chloroplasts. Upon reconstitution of this preparation with the membrane lipids purified from spinach thylakoid...A lipid_depleted cytochrome b 6f (Cyt b 6f) preparation was obtained from spinach (Spinacia oleracea L.) chloroplasts. Upon reconstitution of this preparation with the membrane lipids purified from spinach thylakoid, the effects of different membrane lipids on the electron transfer activity were studied. The results show that the electron transfer activity of Cyt b 6f is obviously stimulated to different extents, respectively, by monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), phosphatidylcholine (PC), phosphatidylglycerol (PG) and sulfoquinovosyldiacylglycerol (SQDG), and that the extents of stimulation may be closely related to the charge of the membrane lipids. The stimulation of non_charged lipids (MGDG, DGDG) and neutrally_charged lipid (PC) was high with a maximum enhancement of 89%, 75% and 77%, respectively; but the stimulation of two kinds of negatively_charged lipid (PG and SQDG) was relatively low with a maximum enhancement of 43% and 26%, respectively.展开更多
Artemisinin, a sesquiterpene lactone endoperoxide derived from Artemisia annua L, forms the basis of the most important medicines for treating malaria in use today. In the study, a total of 41 full genes coded cytochr...Artemisinin, a sesquiterpene lactone endoperoxide derived from Artemisia annua L, forms the basis of the most important medicines for treating malaria in use today. In the study, a total of 41 full genes coded cytochrome P450 monooxygenases were identified from NCBI. These genes were classified into 11 families in 3 gene clans according to sequence similarity. One of the first interesting features in sequence alignment was that the CYP82, CYP83 and CYP716 families specific in Arabidopsis genome were present in Artemisia, and the CYP92 specific in rice was also present in Artemisia. The physical and chemical properties and structure characteristics of the identified P450s were studied. The results showed their secondary structures were very similar and their senior structures mainly contained α-helix.展开更多
Cytochrome b_559 in photosystem Ⅱ reaction center was purified from spinach ( Spinacia oleracea L.) and rice ( Oryza sativa L.) by a rapid and simple procedure. Their low temperature fluorescence emission and e...Cytochrome b_559 in photosystem Ⅱ reaction center was purified from spinach ( Spinacia oleracea L.) and rice ( Oryza sativa L.) by a rapid and simple procedure. Their low temperature fluorescence emission and excitation spectra, ultraviolet fluorescence spectra and absolute absorption spectra were presented. The author's purification methods, which enhanced the yield of pure protein and shorted the time for isolation, have several advantages: 1. use of oxygen_evolving PSⅡ core complexes as the starting material in order to avoid disturbing from other cytochromes; 2. isocratic elution of cytochrome b_559 from a DEAE_Sephacel column for eliminating the impurity and yielding the protein in pure state; 3. a simple column procedure for removal of excess Triton X_100. Purified cytochromes b_559 from these species have similar optical spectra and mobility during gel electrophoresis under native conditions. From the results of novel electrophoresis (Tricine_SDS_PAGE), cytochrome b_559 from both spinach and rice reveal two polypeptide bands (apparent molecular weight 9 kD and 4 kD, respectively). By measuring of 77 K fluorescence spectra, it was shown that for the purified cytochrome b_559 there were two excitation peaks at 439 nm and 413 nm, and two emission peaks at 563 nm and 668 nm. This is the first indication that Cyt b_559 is able to emit fluorescence and also transfer excited electrons to chlorophyll. By the use of ultraviolet fluorescence spectra, it was demonstrated for the first time that the location of Trp residue could be in the hydrophobic transmembrane region of cytochrome b_559.展开更多
Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacte...Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacterial cytosine deaminase), CPG2(carboxypeptidase G2) ,and PNP (purine nucleoside phosphorylase), have been known to bear close relations to cancer. Theirspecific expression and influence on the process of tumor initiation, promotion and progressionattract scientists to apply them as a biochemical marker of certain malignant tumor, a predictor ofresponse in cancer chemotherapy; to apply them to drug design, tumor prevention and as adjuvant toradiotherapy or surgery.展开更多
Phylogenetic relationships of 11 bumblebee species,including 5 subgenera:Bombus (5 species),Thoracobombus (3 species),Mendacibombus (1 species),Fervidobombus (1 species) and Pyrobombus (1 species),were analyzed based ...Phylogenetic relationships of 11 bumblebee species,including 5 subgenera:Bombus (5 species),Thoracobombus (3 species),Mendacibombus (1 species),Fervidobombus (1 species) and Pyrobombus (1 species),were analyzed based on the 357?bp mitochondrial cytochrome b gene sequences.There are 65 singleton polymorphic sites and 71 parsimony informative polymorphic sites in this DNA segment,and 45 polymorphic sites within the total 119 translated amino acids segment.Both NJ tree and MP tree show that Mendacibombus (B.avinovielllus) is basal to others,followed by Fervidobombus (B.pensylvanicus);Pyrobombus (B.impatiens) and Bombus are sister subgenera;the subgenus of Bombus is monophyletic,in which B.ignitus diverged first.展开更多
Our objective was to systematically assess the effect of cytochrome P-450（CYP450） inhibitors on pharmacokinetics and safety of voriconazole（VORI）. Cochrane Library, Pub Med, Embase, CNKI, CBM and Wan Fang database...Our objective was to systematically assess the effect of cytochrome P-450（CYP450） inhibitors on pharmacokinetics and safety of voriconazole（VORI）. Cochrane Library, Pub Med, Embase, CNKI, CBM and Wan Fang databases and C linicaltrials.gov were searched up to Jan. 26～（th） 2016. Two reviewers independently identified studies, extracted data and assessed quality of studies. Meta-analysis was performed with Rev Man 5.3, and risk ratios（RRs） and mean differences（MDs） with 95% confidence intervals（CIs） were calculated. A total of 12 studies were included： three crossover randomized controlled trials, three single-arm before-and-after studies and six cohort studies. Compared with non-combination group, the group of VORI plus omeprazole had a significantly higher occurrence of hepatic dysfunction（RR = 4.11, 95% CI 1.12–15.08, P = 0.03）. However, neurologic dysfunction and visual disturbance were not significantly different. Pantoprazole, rabeprazole, cimetidine and contraceptive significantly increased the peak concentration（Cmax） and area under the curve（AUC） of VORI, while indinavir had no significant effect on pharmacokinetics of VORI. The effects of esomeprazole, erythromycin and azithromycin on pharmacokinetic parameters of VORI presented inconsistent results. Co-administration of VORI and CYP450 inhibitors was safe except for omeprazole. Although Cmax and AUC of VORI were increased while co-administered with a couple of CYP450 inhibitors, no significant effect on clinical outcomes was observed.展开更多
The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulate...The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulates the supply of variable ATP demands in cells by“allosteric ATP-inhibition of CytOx.”This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix via cooperative interaction of the two substrate binding sites in dimeric CytOx.The mechanism keeps mitochondrial membrane potentialΔΨm and reactive oxygen species(ROS)formation at low healthy values.Stress signals increase cytosolic calcium leading to Ca^2+-dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATPinhibition and monomerization of CytOx.This is followed by increase ofΔΨm and formation of ROS.A hypothesis is presented suggesting a dynamic change of binding of NDUFA4,originally identified as a subunit of complex I,between monomeric CytOx(active state with highΔΨm,high ROS and low efficiency)and complex I(resting state with lowΔΨm,low ROS and high efficiency).展开更多
Objective： To analyze the differentially expressed genes （DEGs） among hepatocellular carcinoma （HCC）, para-cancerous tissue （PCT） and normal liver tissue （NLT） by using hgilent microarray and explore the targ...Objective： To analyze the differentially expressed genes （DEGs） among hepatocellular carcinoma （HCC）, para-cancerous tissue （PCT） and normal liver tissue （NLT） by using hgilent microarray and explore the target genes related to the development and progression of HCC. Methods： Total RNA of matched HCC, PCT and NLT of HCC patients was isolated using one step Trizol method and qualified using Lab-onchip method, cRNAs were synthesized, fluoresce labeled and purified after total RNAs purified. The RNAs of HCC and NLT, HCC and PCT were hybridized to Agilent microarray （21 074 probes） respectively. The fluorescence intensities were detected by Agilent scanner and quantified by Feature Extraction software. The DEGs which both differentially expressed in HCC vs NLT and HCC vs PCT were selected as candidate genes and confirmed by SYBR Green I stained real time RT-PCR. Results： （1） The total RNAs, reverse transcription products and fluoresce labeled cRNAs were of high quality; （2） There were 420 up-regulated genes and 552 down-regulated genes in 2-fold DEGs, including 23 genes related to cytochrome P450; （3） CYP2C8 was selected as a candidate gene of 10-fold down-regulated genes. The results of real time RTPCR, using β-actin as an internal control, revealed that the 2^-ΔCt values of CYP2C8 in HCC, PCT and NLT were 0.009383, 0.316812 and 0.607182, respectively. Conclusion： （1） The high throughput and effective Agilent oligomicroarray can screen novel therapy target genes by analyzing the DGEs in development and progression of HCC; （2） The development and progression of HCC is a complicated process involving multigenes and multiprocedures; （3） Down-regulated expression of cytochrome P450 related genes maybe involved in the development and progression of HCC due to the increased activity of certain carcinogens and maybe the exact mechanism need further study.展开更多
S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death...S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.展开更多
The cytochrome P450 （CYP） superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple...The cytochrome P450 （CYP） superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple metabolic pathways with distinct and complex functions, playing important roles in a vast array of reactions. As a result, numerous secondary metabolites are synthesized that function as growth and developmental signals or protect plants from various biotic and abiotic stresses. Here, we summarize the characterization of CYPs, as well as their phylogenetic classification. We also focus on recent advances in elucidating the roles of CYPs in mediating plant growth and development as well as biotic and abiotic stresses responses, providing insights into their potential utilization in plant breeding.展开更多
To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and S...To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.展开更多
基金supported by the Sichuan Province International Science and Technology Innovation Cooperation(2024YFHZ0299)the Project of Science and Technology Department of Sichuan Province(2022YFH0031)Chengdu Science and Technology Bureau(2024-YF05-02168-SN).
文摘Rice sheath blight(RSB)is a major destructive disease impeding rice production.Identifying key germplasm resources with increased resistance remains a challenge.However,the mechanisms underlying disease resistance are not yet fully understood.Cytochrome P450 monooxygenases(CYP450s)serve biosynthesis and metabolic detoxification functions in plants,but there is limited information about their role in the response induced by RSB.This study demonstrated that CYT02 belongs to the CYP73A100 subfamily and is a typical member of the CYP450s.Overexpression(OE)in rice of the cytochrome P450 monooxygenase cyt02 conferred increased resistance to RSB and increased vegetative tillering.Cyt02 may increase RSB resistance by regulating plant hormone synthesis,regulate reactive oxygen species(ROS)by coordinating the activity of antioxidant enzymes,and initiate phytoalexin synthesis in response to fungal infection.These research findings have laid a foundation for a deeper understanding of the function of cyt02 and offered a potential target gene for breeding rice varieties resistant to sheath blight.
基金Supported by the Natural Science Foundation of Hebei Province Beijing-Tianjin-Hebei Basic Research Special Program,No.H2020110287Key Laboratory for Diabetic Kidney Disease Syndrome and Treatment of the Traditional Chinese Medicine Administration of Hebei Province,No.7[2024]+2 种基金Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio,No.3[2024]Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications,No.SZX2020015Jiangsu Province Chinese Medicine Science and Technology Development Program Project,No.YB2020065.
文摘BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effective treatment options remain limited.AIM To evaluate the therapeutic impact of Shenzhuo formulation(SZF)on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.METHODS We established a DN mouse model through a high-fat diet combined with streptozotocin(STZ)injection,followed by SZF treatment.We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques.Additionally,based on transcriptomic and non-targeted metabolomic findings,we further assessed SZF’s influence on the expression of factors related to the cytochrome P450(CYP450)-mediated arachidonic acid(AA)metabolism pathway,as well as its effects on inflammation and oxidative stress.RESULTS SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice.Pathological analysis revealed that SZF treatment improved renal tissue damage,reduced fibrosis,and diminished glycogen deposition.Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes,including Cyp2j13,Cyp2b9,Pla2 g2e/Cyp4a12a,Cyp4a32,Cyp2e1,and Cyp4a14.Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway,including 5,6-EET,14,15-EET,phosphatidylcholine,and 20-HETE.Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue,as well as CYP2J and CYP2B proteins.Additionally,SZF significantly reduced the expression of inflammatory factors in renal tissue,enhanced antioxidant enzyme activity,and alleviated oxidative stress.CONCLUSION SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism,leading to improved renal function and improved pathological state in DN mice.
文摘The cytochrome P4503A(CYP3A)gene family’s role in early progression of gastric cancer was comprehensively investigated.Its potential as a therapeutic target was evaluated.Upon literature review,aberrant expression of the CYP3A gene family has a strong correlation with gastric cancer onset,although the precise underlying mechanisms remain unclear.To assess its potential as a biomarker for early diagnosis and a therapeutic target,we have provided a comprehensive review of the regulatory mechanisms governing CYP3A gene family expression in gastric cancer,as well as its relation with early tumor progression and the tumor microenvironment.The CYP3A gene family is crucial in the proliferation,migration,and invasion of gastric cancer cells and promotes cancer progression by modulating inflammatory responses and oxidative stress within the tumor microenvironment.Furthermore,genetic polymorphisms in CYP3A enzymes highlight its potential value in personalized medicine.Based on these findings,this paper explores the feasibility of developing inhibitors and activators targeting CYP3A enzymes and discusses potential applications in gene therapy.This research provides crucial theoretical support for the CYP3A gene family as an early diagnostic marker and therapeutic target for gastric cancer.In the future,multi-omics studies and large-scale clinical trials will be essential to advance clinical translation of these findings.
基金partly supported by research grants from the Outstanding Youth Foundation of the Beijing Academy of Agriculture and Forestry Sciences,China(YXQN202301)the National Natural Science Foundation of China(32272522)the Beijing Natural Science Foundation,China(6232005)。
文摘The tobacco whitefly,Bemisia tabaci,is a notorious pest affecting various crops globally,and it exhibits high levels of resistance to various insecticides.Afidopyropen is a recently commercialized pyropene insecticide for B.tabaci control with high selectivity and a novel mode of action.We previously identified a high level of afidopyropen resistance in a field-collected population after selection in the lab,and named it the HD-Afi strain.In the present study,minimal cross-resistance in the HD-Afi strain was found between afidopyropen and other common chemical agents.However,the P450 enzyme activity in HD-Afi was 2.18 times the level in susceptible strain HD-S.Expression analysis revealed that two of 12 candidate P450 genes,namely CYP6DW3 and CYP4C64,were significantly up-regulated in HD-Afi.Silencing CYP6DW3 and CYP4C64 by RNA interference(RNAi)substantially increased the susceptibility of whitefly adults,confirming their involvement in afidopyropen resistance.Homology modeling and molecular docking analyses demonstrated stable binding of afidopyropen to CYP6DW3 and CYP4C64,with binding free energies of–6.87 and–6.11 kcal mol^(-1),respectively.The findings of this study suggest that the induction of CYP6DW3 and CYP4C64 facilitates afidopyropen detoxification,contributing to the development of resistance in B.tabaci.
基金support from the National Natural Science Foundation of China(8227131503).
文摘Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework.
文摘BACKGROUND Kidney transplantation is an effective renal replacement therapy for improving survival and quality of life in chronic kidney disease patients.Kidney transplant recipients need lifelong immunosuppression to prevent rejection and allograft dysfunction.Tacrolimus,a calcineurin inhibitor,is metabolized differently based on cytochrome P4503A(CYP3A)5 genetic variations and this impacts the graft outcome.AIM To examine the clinical outcomes in kidney transplant recipients affected by the variable metabolism of tacrolimus due to the CYP3A5 genetic variation,emphasizing personalized immunosuppression strategies to optimize efficacy,minimize toxicity,and enhance long-term graft survival.METHODS A retrospective study was conducted at a tertiary care center in Central India on 95 kidney transplant recipients.Patient demographics,medical history,CYP3A5 polymorphism,post-transplant investigations,graft biopsy results,preexisting comorbidities,history of post–kidney transplant infections,and new onset diabetes after transplantation(NODAT)was collected.Tacrolimus was initiated at 0.1 mg/kg/day for CYP3A5 expressors and 0.05 mg/kg/day for non-expressors,with dose adjustments to maintain target C0 levels of 7-10 ng/mL for first 6 months and 5-7 ng/mL from 6 months to 12 months posttransplant.Patients were followed regularly for one year for glomerular filtration rate(GFR),creatinine,and the tacrolimus trough concentration(ng/mL)/daily tacrolimus dose(mg/kg/day)ratio(C/D).A P value≤0.05 was considered statistically significant.RESULTS Kidney transplant recipients were classified as expressors(CYP3A51 carriers,n=35)and non-expressors(CYP3A5*3*3,n=60).Both groups were comparable for age,sex,and donor characteristics.Tacrolimus dose was comparable post-transplant except at 6 months and 12 months,where expressors required higher doses.Kidney function(creatinine and estimated GFR),NODAT,hypomagnesemia,and infections showed no significant differences between the two groups over 12 months of follow-up.Biopsy-proven acute rejection(BPAR)was found to be more in expressors(22.9%vs 13.3%,P=0.2340)though it was not found to be statistically significant.Nonexpressors had a significantly higher tacrolimus levels and C/D ratio at multiple follow-ups.CONCLUSION CYP3A5 expressors require higher tacrolimus doses to maintain therapeutic levels as compared to non-expressors.BPAR was higher in expressors but the difference was not significant.Graft function,infection rate,and NODAT were comparable irrespective of CYP3A5 expression status,emphasizing the importance of pretransplant CYP3A5 genotyping and therapeutic drug monitoring to guide tacrolimus dosing for individualized immunosuppressive management.
基金This work was supported by the National Natureal Sciences Foundation of China(No: 30571323).
文摘Thirty-three mutations and four different haplotypes were found when cytochrome b（Cytb） gene partial sequences of 12 gayals were analyzed. Together with sequences of Bos indicus, Bos taurus, Bos grunniens, and Bos gaurus with Bubalus bubalis as the out group, the partial sequences of Cytb gene of gayals were aligned and base composition and nucleotide variation of Cytb gene were analyzed. The phylogenetic trees were constructed by the NJ method and the MP method respectively, both supporting almost the same topology. Gayal is an independent species of Bos from Bos indicus, Bos taurus, and Bos gaurus. The results also indicate that a great proportion of gayal bloodline was invaded by other species, and the protection of gayal is facing a formidable situation.
基金Supported by National Natural Science Foundation of China(30770263)~~
文摘[Objective] The aim was to explore the phylogenetic relationships among four subspecies of the genus Locusta.[Method] The sequences of three subunits of cytochrome oxidase of Locusta migratoria tibetensis and Locusta migratoria manilensis were amplified and sequenced（COⅠ 1 539 bp,COⅡ 684 bp,CO Ⅲ 792 bp,with the total of 3 015 bp）.The corresponding sequenses of Locusta migratoria migratoria and Locusta migratoria migratorioides were obtained from GenBank and constructed a multiple alignment.Phylogenic trees of four subspecies of L.migratoria were constructed by Neighbor-Joining,Maximum-parsimony and Bayesian,respectively.[Result] The average content of A ＋ T in three subunits of four subspecies was 69.57%;the third site of codon showed the highest A ＋ T content,and the COⅠ had the highest A ＋ T content（87.6%）;The nucleotide substitution mainly occurred at the third site of codon,and the nucleotide replacement rate of CO Ⅱ was the highest.The second site of codon was conservative,so the replacement rate was in the range of 5.9%-15%.The start codon of COⅠ was CCG or ACG.Genetic distances among four subspecies were ranged from 0.001 to 0.076.The relationship between L.m.tibetensis and Locusta migratoria manilensis was the closest,followed by L.m.migratorioides and L.m.migratorioides,while the genetic distance between L.m.tibetensis and L.m.migratorioides was the largest.[Conclusion] The phylogenetic relationships among four subspecies of Locusta migratoria is L.m.tibetensis,L.m.manilensis,L.m.migratoria,L.m.migratorioides.
基金The State Key Basic Research and Development Plan(G1998010100)Innovative Foundation of Laboratory of Photosynthesis Basic Research Insitute of Botany,The Chinese Academy of Sciences
文摘A lipid_depleted cytochrome b 6f (Cyt b 6f) preparation was obtained from spinach (Spinacia oleracea L.) chloroplasts. Upon reconstitution of this preparation with the membrane lipids purified from spinach thylakoid, the effects of different membrane lipids on the electron transfer activity were studied. The results show that the electron transfer activity of Cyt b 6f is obviously stimulated to different extents, respectively, by monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), phosphatidylcholine (PC), phosphatidylglycerol (PG) and sulfoquinovosyldiacylglycerol (SQDG), and that the extents of stimulation may be closely related to the charge of the membrane lipids. The stimulation of non_charged lipids (MGDG, DGDG) and neutrally_charged lipid (PC) was high with a maximum enhancement of 89%, 75% and 77%, respectively; but the stimulation of two kinds of negatively_charged lipid (PG and SQDG) was relatively low with a maximum enhancement of 43% and 26%, respectively.
文摘Artemisinin, a sesquiterpene lactone endoperoxide derived from Artemisia annua L, forms the basis of the most important medicines for treating malaria in use today. In the study, a total of 41 full genes coded cytochrome P450 monooxygenases were identified from NCBI. These genes were classified into 11 families in 3 gene clans according to sequence similarity. One of the first interesting features in sequence alignment was that the CYP82, CYP83 and CYP716 families specific in Arabidopsis genome were present in Artemisia, and the CYP92 specific in rice was also present in Artemisia. The physical and chemical properties and structure characteristics of the identified P450s were studied. The results showed their secondary structures were very similar and their senior structures mainly contained α-helix.
文摘Cytochrome b_559 in photosystem Ⅱ reaction center was purified from spinach ( Spinacia oleracea L.) and rice ( Oryza sativa L.) by a rapid and simple procedure. Their low temperature fluorescence emission and excitation spectra, ultraviolet fluorescence spectra and absolute absorption spectra were presented. The author's purification methods, which enhanced the yield of pure protein and shorted the time for isolation, have several advantages: 1. use of oxygen_evolving PSⅡ core complexes as the starting material in order to avoid disturbing from other cytochromes; 2. isocratic elution of cytochrome b_559 from a DEAE_Sephacel column for eliminating the impurity and yielding the protein in pure state; 3. a simple column procedure for removal of excess Triton X_100. Purified cytochromes b_559 from these species have similar optical spectra and mobility during gel electrophoresis under native conditions. From the results of novel electrophoresis (Tricine_SDS_PAGE), cytochrome b_559 from both spinach and rice reveal two polypeptide bands (apparent molecular weight 9 kD and 4 kD, respectively). By measuring of 77 K fluorescence spectra, it was shown that for the purified cytochrome b_559 there were two excitation peaks at 439 nm and 413 nm, and two emission peaks at 563 nm and 668 nm. This is the first indication that Cyt b_559 is able to emit fluorescence and also transfer excited electrons to chlorophyll. By the use of ultraviolet fluorescence spectra, it was demonstrated for the first time that the location of Trp residue could be in the hydrophobic transmembrane region of cytochrome b_559.
文摘Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacterial cytosine deaminase), CPG2(carboxypeptidase G2) ,and PNP (purine nucleoside phosphorylase), have been known to bear close relations to cancer. Theirspecific expression and influence on the process of tumor initiation, promotion and progressionattract scientists to apply them as a biochemical marker of certain malignant tumor, a predictor ofresponse in cancer chemotherapy; to apply them to drug design, tumor prevention and as adjuvant toradiotherapy or surgery.
文摘Phylogenetic relationships of 11 bumblebee species,including 5 subgenera:Bombus (5 species),Thoracobombus (3 species),Mendacibombus (1 species),Fervidobombus (1 species) and Pyrobombus (1 species),were analyzed based on the 357?bp mitochondrial cytochrome b gene sequences.There are 65 singleton polymorphic sites and 71 parsimony informative polymorphic sites in this DNA segment,and 45 polymorphic sites within the total 119 translated amino acids segment.Both NJ tree and MP tree show that Mendacibombus (B.avinovielllus) is basal to others,followed by Fervidobombus (B.pensylvanicus);Pyrobombus (B.impatiens) and Bombus are sister subgenera;the subgenus of Bombus is monophyletic,in which B.ignitus diverged first.
基金The Medical Education Research Project from Society of Medical Education and Medical Education Committee of China Association of Higher Education(Grant No.2016B-YX007)
文摘Our objective was to systematically assess the effect of cytochrome P-450（CYP450） inhibitors on pharmacokinetics and safety of voriconazole（VORI）. Cochrane Library, Pub Med, Embase, CNKI, CBM and Wan Fang databases and C linicaltrials.gov were searched up to Jan. 26～（th） 2016. Two reviewers independently identified studies, extracted data and assessed quality of studies. Meta-analysis was performed with Rev Man 5.3, and risk ratios（RRs） and mean differences（MDs） with 95% confidence intervals（CIs） were calculated. A total of 12 studies were included： three crossover randomized controlled trials, three single-arm before-and-after studies and six cohort studies. Compared with non-combination group, the group of VORI plus omeprazole had a significantly higher occurrence of hepatic dysfunction（RR = 4.11, 95% CI 1.12–15.08, P = 0.03）. However, neurologic dysfunction and visual disturbance were not significantly different. Pantoprazole, rabeprazole, cimetidine and contraceptive significantly increased the peak concentration（Cmax） and area under the curve（AUC） of VORI, while indinavir had no significant effect on pharmacokinetics of VORI. The effects of esomeprazole, erythromycin and azithromycin on pharmacokinetic parameters of VORI presented inconsistent results. Co-administration of VORI and CYP450 inhibitors was safe except for omeprazole. Although Cmax and AUC of VORI were increased while co-administered with a couple of CYP450 inhibitors, no significant effect on clinical outcomes was observed.
文摘The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulates the supply of variable ATP demands in cells by“allosteric ATP-inhibition of CytOx.”This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix via cooperative interaction of the two substrate binding sites in dimeric CytOx.The mechanism keeps mitochondrial membrane potentialΔΨm and reactive oxygen species(ROS)formation at low healthy values.Stress signals increase cytosolic calcium leading to Ca^2+-dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATPinhibition and monomerization of CytOx.This is followed by increase ofΔΨm and formation of ROS.A hypothesis is presented suggesting a dynamic change of binding of NDUFA4,originally identified as a subunit of complex I,between monomeric CytOx(active state with highΔΨm,high ROS and low efficiency)and complex I(resting state with lowΔΨm,low ROS and high efficiency).
基金This study was supported by key research project of "135" engineer of Jiangsu Province.
文摘Objective： To analyze the differentially expressed genes （DEGs） among hepatocellular carcinoma （HCC）, para-cancerous tissue （PCT） and normal liver tissue （NLT） by using hgilent microarray and explore the target genes related to the development and progression of HCC. Methods： Total RNA of matched HCC, PCT and NLT of HCC patients was isolated using one step Trizol method and qualified using Lab-onchip method, cRNAs were synthesized, fluoresce labeled and purified after total RNAs purified. The RNAs of HCC and NLT, HCC and PCT were hybridized to Agilent microarray （21 074 probes） respectively. The fluorescence intensities were detected by Agilent scanner and quantified by Feature Extraction software. The DEGs which both differentially expressed in HCC vs NLT and HCC vs PCT were selected as candidate genes and confirmed by SYBR Green I stained real time RT-PCR. Results： （1） The total RNAs, reverse transcription products and fluoresce labeled cRNAs were of high quality; （2） There were 420 up-regulated genes and 552 down-regulated genes in 2-fold DEGs, including 23 genes related to cytochrome P450; （3） CYP2C8 was selected as a candidate gene of 10-fold down-regulated genes. The results of real time RTPCR, using β-actin as an internal control, revealed that the 2^-ΔCt values of CYP2C8 in HCC, PCT and NLT were 0.009383, 0.316812 and 0.607182, respectively. Conclusion： （1） The high throughput and effective Agilent oligomicroarray can screen novel therapy target genes by analyzing the DGEs in development and progression of HCC; （2） The development and progression of HCC is a complicated process involving multigenes and multiprocedures; （3） Down-regulated expression of cytochrome P450 related genes maybe involved in the development and progression of HCC due to the increased activity of certain carcinogens and maybe the exact mechanism need further study.
基金Supported by NIH/NIAAA Grants No. AA017425Supported by NIH/NIAAA Grants No. AA018790
文摘S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.
基金financially supported in part by National Natural Science Foundation of China (31171590)funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (010-809001)Jiangsu Collaborative Innovation Center for Modern Crop Production, China (No.10)
文摘The cytochrome P450 （CYP） superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple metabolic pathways with distinct and complex functions, playing important roles in a vast array of reactions. As a result, numerous secondary metabolites are synthesized that function as growth and developmental signals or protect plants from various biotic and abiotic stresses. Here, we summarize the characterization of CYPs, as well as their phylogenetic classification. We also focus on recent advances in elucidating the roles of CYPs in mediating plant growth and development as well as biotic and abiotic stresses responses, providing insights into their potential utilization in plant breeding.
基金supported by grants from the National Natural Science Foundation of China(No.81274127,No.81073149)the National Basic Research Program("973 Program")of China(No.2012CB518402,No.2011CB505304)
文摘To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.
