Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is ...Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is orchestrated by the interplay between iron,lipid peroxides,and glutathione.In this review,we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis,including iron intake and export as well as ferritinophagy,and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases,especially P450 oxidoreductases,in modulating LPO.We summarize how various types of fatty acids(FAs),including saturated,monounsaturated,and polyunsaturated FAs,differentially influence ferroptosis when incorporated into phospholipids.Furthermore,we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis,shedding light on therapeutic avenues for ferroptosis-associated diseases.展开更多
Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an imp...Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.展开更多
Ferroptosis is a new regulated cell death process executed by lipid peroxidation(LPO)of polyunsaturated fatty acids.Lipid droplets(LDs),as an important organelle for lipid storage and metabolism,are probably a major s...Ferroptosis is a new regulated cell death process executed by lipid peroxidation(LPO)of polyunsaturated fatty acids.Lipid droplets(LDs),as an important organelle for lipid storage and metabolism,are probably a major site of LPO and play critical roles in the regulation of ferroptosis.However,the detailed study on LPO in LDs has not been carried out because of the lack of LD-targeting tools for the in situ monitoring of LPO.Herein,the first LD-targeting LPO fluorescence probe(LD-LPO)has been developed.LD-LPO exhibits a rapid and selective fluorescence enhancement at 518 nm,which is unaffected by highly destructive reactive oxygen species(e.g.,hydroxyl radical)and environmental factor changes(e.g.,polarity and viscosity).LD-LPO is capable of targeting LDs and visualizing LPO within LDs in situ during erastin-or(1S,3R)-RSL3(RSL3)-induced ferroptosis.Moreover,LD-LPO has also been used to image LPO in the ferroptosis-associated non-alcoholic fatty liver disease(NAFLD),and to evaluate the medicine treatment of NAFLD with saroglitazar,demonstrating its utility for monitoring LPO levels in biosystems.The favorable analytical and imaging performance of LD-LPO may allow its application in more ferroptosisassociated physiological and pathological processes.展开更多
Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics anal...Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure.DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability,apoptosis,and lipid peroxidation.The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays.Cardiac function was assessed by echocardiography,and biochemical markers of heart failure were measured using ELISA.The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.Results miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts.Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis,lipid peroxidation,and cardiac dysfunction.ACSM1 was identified as a direct target of miR-144-5p,and its expression was downregulated by DOX.Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability,apoptosis,and lipid peroxidation of cardiomyocytes.Furthermore,miR-144-5p inhibition improved cardiac function in DOX-treated mice,as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers(BNP,LDH,Ang II,and ALD).Conclusions Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation.The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure.Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.展开更多
Objective To explore the protective effects and underlying mechanisms of H_(2)S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.Methods Cell viability was evaluated using CCK-8...Objective To explore the protective effects and underlying mechanisms of H_(2)S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.Methods Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2(Nrf2), and cystathionine β-synthase(CBS) expression were determined using western blotting or real-time PCR. Sulforaphane(SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression.Results GYY4137(an H_(2)S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uraniumdecreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes.Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability.Conclusion H_(2)S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H_(2)S axis. Simultaneously, the Nrf2-controlled CBS/H_(2)S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycleregulating mode through which H_(2)S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.展开更多
Lipid peroxidation(LPO)in foam cells is crucial for regulating atherosclerosis progression.It correlates with lipid uptake and the state of lipid droplets.In this study,we report a lipid droplet-targeted fluorescent L...Lipid peroxidation(LPO)in foam cells is crucial for regulating atherosclerosis progression.It correlates with lipid uptake and the state of lipid droplets.In this study,we report a lipid droplet-targeted fluorescent LPO probe,Ld-LPO.It selectively responds to LPO,resulting in a significant fluorescence shift from 590 to 525 nm,enabling a ratiometric imaging of LPO in lipid droplets.Ld-LPO traces lipid droplets in foam cells,revealing a correlation between LPO and lysosomal engulfment.We found that lipid droplets engulfed by lysosomes exhibit higher LPO,attributed to low-density lipoprotein accumulation in lysosomes.Furthermore,Ld-LPO is compatible with dual-color flow cytometry,facilitating highthroughput analysis of LPO in foam cells.展开更多
[Objective] The aim of this study was to investigate the characteristics and mechanism of chemical emasculation in rapeseed and to provide the theoretical basis for development and utilization of new chemical gametoci...[Objective] The aim of this study was to investigate the characteristics and mechanism of chemical emasculation in rapeseed and to provide the theoretical basis for development and utilization of new chemical gametocides.[Method] The activity of peroxidase,catalase and the content of hydrogen peroxide,malondialdehyde in leaves and flower buds of Brassica napus cultivars Qinyou No.3 and L89 induced by the chemical gametocide EXP in the course of male sterility were studied.[Result] Protective enzyme activity and the content of hydrogen peroxide,malondialdehyde in rapeseed treated with EXP changed significantly,which indicated that active oxygen metabolism was abnormal.Furthermore,there was a significant difference in the reaction degree of different cultivars and organs treated by EXP.[Conclusion] There was a correlation between the disturbance of active oxygen metabolism and the male sterility induced by chemical gametocide EXP.展开更多
With indica ( Oryza sativa L.) hybrid Shanyou 63 as control, the hybrid rice varieties including Peiai 64S/E32, Peiai 64S/9311, X07S/Zihui 100, Guangyou 881 and japonica 9516 were used to study changes of chlorophyll ...With indica ( Oryza sativa L.) hybrid Shanyou 63 as control, the hybrid rice varieties including Peiai 64S/E32, Peiai 64S/9311, X07S/Zihui 100, Guangyou 881 and japonica 9516 were used to study changes of chlorophyll content, photosynthetic response to light intensity and temperature, chlorophyll fluorescence characteristics and membrane lipid peroxidation in their flag leaves at the late stage of development under natural conditions in Nanjing. The results were as follows:. primary photochemical efficiency of PS II ( F-v / F-m), quantum yield of linear electron transport of PS II (phi(PSII)), electron transfer rate (ETR) in these rice varieties decreased with their decrease of chlorophyll content during this period. This kind of impediment to energy conversion induced the transfer of excessive energy to the reducing side of PS I, hence the accumulation of O-2(radical anion) and peroxidation of membrane lipid, and resulting in the accumulation of malondialdehyde (MDA), that is the destroys of photosynthetic pigments and membranes and the consequent, premature senescence. This phenomenon is variable conspicuously in different rice varieties. Under natural condition in Nanjing, F-v/F-m, phi(PSII), ETR and quenching coefficient ( qP) in japonica 9516 tolerant to photooxidation decreased less and the conversion capacity of light energy was stable, premature senescence was unlikely, and consequently the seed-setting rate was higher. While F-v/F-m, phi(PSII), ETR and photochemical qP in Shanyou 63 sensitive to photooxidation decreased more and therefore premature senescence was easy to happen, thus the seed-setting rate and yield were all reduced. The tolerance to photooxidation and premature senescence in other hybrids derived from typical two line or three line crossing laid in the middle. From the rice breeding for super-high-yield, on the basis of the good plant-type of current rice, considering both hybrid vigor and the prevention premature senescence, it would be a notable strategy to use japonica maternal line or maternal. lines with some japonica genotype as the sterile lines in rice breeding.展开更多
[ Objective] The aim was to provide strategies for development of rare earth and control of environmental pollution. [ Method] Responses of membrane lipid peroxidation and endogenous hormones of soybean seedlings to U...[ Objective] The aim was to provide strategies for development of rare earth and control of environmental pollution. [ Method] Responses of membrane lipid peroxidation and endogenous hormones of soybean seedlings to UV-B radiation and rare earth were studied through hydroponics in laboratory. [ Result] The results showed that under irradiation of UV-B（ T1-0.15 W/m^2 and T2-0.45 W/m^2）, chlorophyll and indole-3-acetic acid（IAA） contents firstly decreased during the stress phase （1 -5 d） and then increased during the restoration phase （6 -9 d） while contents of malonadialdehyde（MDA） and abscisic acid（ABA） gradually increased during the imposition of UV-B radiation （1 -5 d） and subsequently decreased during recovery from UV-B stress （6 -9 d） . With adding of La （III） with the concentration of 20 mg · L^-1 , the decline/dse trend of chlorophyll, IAA, MDA and ABA contents was slowed down during the stress period while the rise/decline speed was accelerated during the recovery period. [ Conclusion] It suggests that the regulation of La （ III ） on membrane lipid peroxidation and endogenous hormones could increase chlorophyll and IAA contents, improve the metabolism of reactive oxygen species （ ROS）, inhibit membrane lipid peroxidation, decrease the accumulation amount of ABA and alleviate injury of UV-B radiation to soybean seedlings. Further, the protective potential of La （ III ） was better under low UV-B radiation than under high one.展开更多
AIM To study the protective effects of tea polyphenol (TP) on cerebral ischemia reperfusion injury in rats and its scavenging oxygen free radical(OFR) activities and antilipid peroxidation in vitro . METHODS Cer...AIM To study the protective effects of tea polyphenol (TP) on cerebral ischemia reperfusion injury in rats and its scavenging oxygen free radical(OFR) activities and antilipid peroxidation in vitro . METHODS Cerebral ischemia reperfusion injury was produced by bilateral ligation of the common carotid arteries with vagus nerves and reperfusion for 45 min. The mitochondrial lipid peroxidation of rat brain induced by oxygen free radical was measured by thiobarbituric acid spectrophotometry. Superoxide anion (O 2) from xanthine xanthine oxidase system and hydroxyl radical (·OH) from Fe 2+ -H 2O 2 system were determined with spectrophotometry. RESULTS During Cerebral ischemia reperfusion,TP improved the activities of superoxide dismutase ( P 【0 05), GSH peroxidase( P 【0 01) and catalase( P 【0 01), while decreasing the maiondialdchyde content in the brain( P 【0 05) and brain water content ( P 【0 01). Tea polyphenol possessed significantly scavenging effects on ·OH produced by Fenton reaction and O 2 produced by xanthine xanthine oxidase system (the IC 50 were 2 2 mmol·L -1 and 1 9 mmol·L -1 respectively). Tea polyphenol could significant inhibit the lipid peroxidation of cerbral mitochondrial membrane induced by ·OH in a concentration dependent manner. CONCLUSION The results indicate that tea polyphenol could protect the injury on cerebral ischemia reperfusion in rats for OFR, these effects may be related to its scavenging effects on oxygen free radicals and antilipid peroxidant.展开更多
The effect of weak light on the peroxidation of membrane_lipid of one_year_old cherries ( Prunus pseudocerasus L. 'Laiyang') was studied by whole_tree shading. The results showed that the net photosynthetic...The effect of weak light on the peroxidation of membrane_lipid of one_year_old cherries ( Prunus pseudocerasus L. 'Laiyang') was studied by whole_tree shading. The results showed that the net photosynthetic rate of cherry leaves under weak light was remarkably lower; the activity peroxidase (POD) increased when light intensity decreased; the activity of catalase (CAT) showed an opposite trend, and it was positively correlated with light intensity; the activity of superoxide dismutase (SOD) increased under 366 μmol·m -2 ·s -1 and 533.8 μmol·m -2 ·s -1 light intensity, but decreased under 228.8 μmol·m -2 ·s -1 and 83.9 μmol·m -2 ·s -1 light intensity. A remarkable increase of malondialdehyde (MDA), a product of membrane_lipid peroxidation, was also observed in cherry leaves when treated with weak light, indicating more serious peroxidation in the membrane.展开更多
Relationships between fluorescence parameters and membrane lipid peroxidation in leaves of indica and japonica rice (Oryza sativa L.) during later growth stage were studied under chilling temperature and strong light ...Relationships between fluorescence parameters and membrane lipid peroxidation in leaves of indica and japonica rice (Oryza sativa L.) during later growth stage were studied under chilling temperature and strong light stress conditions. Results showed that D1 protein contents of PSⅡ in photosynthetic apparatus dropped, the generation of antheraxanthin (A) and zeaxanthin (Z) of xanthophyll cycle were inhibited partly, PSⅡ photochemical efficiency (F v/F m)and non-photochemical quenching (q N) were also decreased obviously. In addition, endogenous active oxygen scavenger—superoxide dismutase (SOD) reduced, superoxide anion radical (O -· 2) and malondialdehyde (MDA) accumulated, as a result, photooxidation of leaves occurred under chilling temperature and strong light stress conditions. Obvious differences in the changes of the above mentioned physiological parameters between indica and japonica rice were observed. Experiments in leaves treated with inhibitors under chilling temperature and strong light conditions showed that indica rice was more sensitive to chilling temperature with strong light and subjected to photooxidation more than japonica rice. Notable positive correlation between D1 protein contents and F v/F m or (A+Z)/(A+Z+V), and a marked negative correlation between F v/F m and MDA contents were obtained by regression analysis in indica and japonica rice during chilling temperature and strong light conditions. According to the facts mentioned above, it was inferred that PSⅡ photochemical efficiency(F v/F m) was the key index to forecast for the prediction of photooxidation under stress circumstances and the physiological basis were the synthetic capacity of D1 protein and the protection of xanthophyll cycle.展开更多
Using various high-yield rices (Oryza sativa L.) such as japonica cultivar 9516, two parental line hybrid rice between subspecies with more japonica element Peiai 64/E32, Liangyoupeijiu (Peiai 64/9311), and indica hyb...Using various high-yield rices (Oryza sativa L.) such as japonica cultivar 9516, two parental line hybrid rice between subspecies with more japonica element Peiai 64/E32, Liangyoupeijiu (Peiai 64/9311), and indica hybrid rices X07S/Zihui 100, Gangyou 881, Shanyou 63 as the materials, the characteristics of chlorophyll fluorescence and membrane-lipid peroxidation of detached leaves at booting stage under photooxidation conditions were studied. In comparison with indica hybrid rice, after the photooxidation treatment, the primary photochemical efficiency of PS II (F-v/F-m), quantum yield of linear electron transport of PS II (Phi(PSII)) and photochemical quenching coefficient (qP) in japonica cultivar and hybrid rice with japonica decreased less. This indicated that high-yield rice with japonica was able to maintain higher capability of light energy conversion, resulting in the alleviation of photoinhibition. Meanwhile, the higher activities of protective enzymes such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) led to the less accumulation of endogenous active oxygen (O-(2)(radical anion), H2O2) and less content of the malondialdehyde (MDA) and the less decline of chlorophyll and protein contents, indicating a stronger tolerance to photooxidation. The changes in contents of chlorophyll and protein among various nee cultivars during photooxidation treatment were consistent with the decline of chlorophyll content from heading stage to maturation stage under natural conditions. Statistical analysis showed that there was a significant correlation between the indexes of tolerance to photooxidation and the rate of seed setting, implying that the cultivar tolerated to photooxidation had higher resistance to early aging of leaf. These results suggested that from a view of superhigh-yield breeding, considering both the utilization of heterosis and the resistance to early aging of leaf, introduction of japonica element tolerating to photooxidation into the rice sterile line (maternal plant) is a breeding strategy worthy to pay great attention to.展开更多
基金supported by grants from the National Natural Science Foundation of China(22076104)the“Taishan Scholars”Program for Young Expert of Shandong Province(tsqn202103105).
文摘Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is orchestrated by the interplay between iron,lipid peroxides,and glutathione.In this review,we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis,including iron intake and export as well as ferritinophagy,and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases,especially P450 oxidoreductases,in modulating LPO.We summarize how various types of fatty acids(FAs),including saturated,monounsaturated,and polyunsaturated FAs,differentially influence ferroptosis when incorporated into phospholipids.Furthermore,we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis,shedding light on therapeutic avenues for ferroptosis-associated diseases.
基金supported by the National Natural Science Foundation of China(82270386,82070252,and 8207025)the Zhejiang Provincial Medical and Health Science and Technology Plan(2023RC020)the Zhejiang Provincial Natural Science Foundation(LR21H020001).
文摘Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.
基金the financial support from the National Natural Science Foundation of China(Nos.82060626,22004137,22164022,22174147,22074151,22374153,22174148)Excellent Youth scientific and technological talents of Guizhou Province(No.Qiankehe platform talents[2021]5638)+3 种基金Talents of Guizhou Science and Technology Cooperation Platform(No.[2020]4104)Science and Technology Innovation Team of Higher Education of Guizhou Provincial Education Department(No.Qianjiaoji[2023]073)Future Science and Technology Elite Talent Cultivation Project of Zunyi Medical University(No.ZYSE-2021-01)Zunyi Science and Technology Plan Project(No.Zunshi Keren Platform[2023]2)。
文摘Ferroptosis is a new regulated cell death process executed by lipid peroxidation(LPO)of polyunsaturated fatty acids.Lipid droplets(LDs),as an important organelle for lipid storage and metabolism,are probably a major site of LPO and play critical roles in the regulation of ferroptosis.However,the detailed study on LPO in LDs has not been carried out because of the lack of LD-targeting tools for the in situ monitoring of LPO.Herein,the first LD-targeting LPO fluorescence probe(LD-LPO)has been developed.LD-LPO exhibits a rapid and selective fluorescence enhancement at 518 nm,which is unaffected by highly destructive reactive oxygen species(e.g.,hydroxyl radical)and environmental factor changes(e.g.,polarity and viscosity).LD-LPO is capable of targeting LDs and visualizing LPO within LDs in situ during erastin-or(1S,3R)-RSL3(RSL3)-induced ferroptosis.Moreover,LD-LPO has also been used to image LPO in the ferroptosis-associated non-alcoholic fatty liver disease(NAFLD),and to evaluate the medicine treatment of NAFLD with saroglitazar,demonstrating its utility for monitoring LPO levels in biosystems.The favorable analytical and imaging performance of LD-LPO may allow its application in more ferroptosisassociated physiological and pathological processes.
基金supported by Chongqing Science and Health Joint Medical Research Project(No.2023MSXM081)2023 Key Disciplines on Public Health Construction in Chongqing.
文摘Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure.DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability,apoptosis,and lipid peroxidation.The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays.Cardiac function was assessed by echocardiography,and biochemical markers of heart failure were measured using ELISA.The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.Results miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts.Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis,lipid peroxidation,and cardiac dysfunction.ACSM1 was identified as a direct target of miR-144-5p,and its expression was downregulated by DOX.Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability,apoptosis,and lipid peroxidation of cardiomyocytes.Furthermore,miR-144-5p inhibition improved cardiac function in DOX-treated mice,as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers(BNP,LDH,Ang II,and ALD).Conclusions Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation.The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure.Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.
基金supported by the National Natural Science Foundation of China(No.82160627)the Natural Science Foundation of the Guangxi Autonomous Region(No.2020GXNFSAA297262)。
文摘Objective To explore the protective effects and underlying mechanisms of H_(2)S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells.Methods Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2(Nrf2), and cystathionine β-synthase(CBS) expression were determined using western blotting or real-time PCR. Sulforaphane(SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression.Results GYY4137(an H_(2)S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uraniumdecreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes.Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability.Conclusion H_(2)S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H_(2)S axis. Simultaneously, the Nrf2-controlled CBS/H_(2)S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycleregulating mode through which H_(2)S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
基金supported by the National Natural Science Foundation of China(No.T2422004,22278059,22174009,and 22078047)Fundamental Research Funds for the Central Universities(No.DUT22LAB601,DUT22LAB608,and DUT24ZD119)the Outstanding Youth Foundation of Liaoning(No.2022-YQ-08).
文摘Lipid peroxidation(LPO)in foam cells is crucial for regulating atherosclerosis progression.It correlates with lipid uptake and the state of lipid droplets.In this study,we report a lipid droplet-targeted fluorescent LPO probe,Ld-LPO.It selectively responds to LPO,resulting in a significant fluorescence shift from 590 to 525 nm,enabling a ratiometric imaging of LPO in lipid droplets.Ld-LPO traces lipid droplets in foam cells,revealing a correlation between LPO and lysosomal engulfment.We found that lipid droplets engulfed by lysosomes exhibit higher LPO,attributed to low-density lipoprotein accumulation in lysosomes.Furthermore,Ld-LPO is compatible with dual-color flow cytometry,facilitating highthroughput analysis of LPO in foam cells.
基金Supported by the Special Research Fund of "National life Science&Technology Training Base" of Northwest A&F University[2006-(1)-061]~~
文摘[Objective] The aim of this study was to investigate the characteristics and mechanism of chemical emasculation in rapeseed and to provide the theoretical basis for development and utilization of new chemical gametocides.[Method] The activity of peroxidase,catalase and the content of hydrogen peroxide,malondialdehyde in leaves and flower buds of Brassica napus cultivars Qinyou No.3 and L89 induced by the chemical gametocide EXP in the course of male sterility were studied.[Result] Protective enzyme activity and the content of hydrogen peroxide,malondialdehyde in rapeseed treated with EXP changed significantly,which indicated that active oxygen metabolism was abnormal.Furthermore,there was a significant difference in the reaction degree of different cultivars and organs treated by EXP.[Conclusion] There was a correlation between the disturbance of active oxygen metabolism and the male sterility induced by chemical gametocide EXP.
文摘With indica ( Oryza sativa L.) hybrid Shanyou 63 as control, the hybrid rice varieties including Peiai 64S/E32, Peiai 64S/9311, X07S/Zihui 100, Guangyou 881 and japonica 9516 were used to study changes of chlorophyll content, photosynthetic response to light intensity and temperature, chlorophyll fluorescence characteristics and membrane lipid peroxidation in their flag leaves at the late stage of development under natural conditions in Nanjing. The results were as follows:. primary photochemical efficiency of PS II ( F-v / F-m), quantum yield of linear electron transport of PS II (phi(PSII)), electron transfer rate (ETR) in these rice varieties decreased with their decrease of chlorophyll content during this period. This kind of impediment to energy conversion induced the transfer of excessive energy to the reducing side of PS I, hence the accumulation of O-2(radical anion) and peroxidation of membrane lipid, and resulting in the accumulation of malondialdehyde (MDA), that is the destroys of photosynthetic pigments and membranes and the consequent, premature senescence. This phenomenon is variable conspicuously in different rice varieties. Under natural condition in Nanjing, F-v/F-m, phi(PSII), ETR and quenching coefficient ( qP) in japonica 9516 tolerant to photooxidation decreased less and the conversion capacity of light energy was stable, premature senescence was unlikely, and consequently the seed-setting rate was higher. While F-v/F-m, phi(PSII), ETR and photochemical qP in Shanyou 63 sensitive to photooxidation decreased more and therefore premature senescence was easy to happen, thus the seed-setting rate and yield were all reduced. The tolerance to photooxidation and premature senescence in other hybrids derived from typical two line or three line crossing laid in the middle. From the rice breeding for super-high-yield, on the basis of the good plant-type of current rice, considering both hybrid vigor and the prevention premature senescence, it would be a notable strategy to use japonica maternal line or maternal. lines with some japonica genotype as the sterile lines in rice breeding.
基金Supported by the Foundation of State Developing and ReformingCommittee(No.IFZ20051210)the National Natural Science Foundationof China(No.30570323,No.20471030)the Programsin Science and Technology of Nantong(No.DE2009006,No.S2009019)~~
文摘[ Objective] The aim was to provide strategies for development of rare earth and control of environmental pollution. [ Method] Responses of membrane lipid peroxidation and endogenous hormones of soybean seedlings to UV-B radiation and rare earth were studied through hydroponics in laboratory. [ Result] The results showed that under irradiation of UV-B（ T1-0.15 W/m^2 and T2-0.45 W/m^2）, chlorophyll and indole-3-acetic acid（IAA） contents firstly decreased during the stress phase （1 -5 d） and then increased during the restoration phase （6 -9 d） while contents of malonadialdehyde（MDA） and abscisic acid（ABA） gradually increased during the imposition of UV-B radiation （1 -5 d） and subsequently decreased during recovery from UV-B stress （6 -9 d） . With adding of La （III） with the concentration of 20 mg · L^-1 , the decline/dse trend of chlorophyll, IAA, MDA and ABA contents was slowed down during the stress period while the rise/decline speed was accelerated during the recovery period. [ Conclusion] It suggests that the regulation of La （ III ） on membrane lipid peroxidation and endogenous hormones could increase chlorophyll and IAA contents, improve the metabolism of reactive oxygen species （ ROS）, inhibit membrane lipid peroxidation, decrease the accumulation amount of ABA and alleviate injury of UV-B radiation to soybean seedlings. Further, the protective potential of La （ III ） was better under low UV-B radiation than under high one.
文摘AIM To study the protective effects of tea polyphenol (TP) on cerebral ischemia reperfusion injury in rats and its scavenging oxygen free radical(OFR) activities and antilipid peroxidation in vitro . METHODS Cerebral ischemia reperfusion injury was produced by bilateral ligation of the common carotid arteries with vagus nerves and reperfusion for 45 min. The mitochondrial lipid peroxidation of rat brain induced by oxygen free radical was measured by thiobarbituric acid spectrophotometry. Superoxide anion (O 2) from xanthine xanthine oxidase system and hydroxyl radical (·OH) from Fe 2+ -H 2O 2 system were determined with spectrophotometry. RESULTS During Cerebral ischemia reperfusion,TP improved the activities of superoxide dismutase ( P 【0 05), GSH peroxidase( P 【0 01) and catalase( P 【0 01), while decreasing the maiondialdchyde content in the brain( P 【0 05) and brain water content ( P 【0 01). Tea polyphenol possessed significantly scavenging effects on ·OH produced by Fenton reaction and O 2 produced by xanthine xanthine oxidase system (the IC 50 were 2 2 mmol·L -1 and 1 9 mmol·L -1 respectively). Tea polyphenol could significant inhibit the lipid peroxidation of cerbral mitochondrial membrane induced by ·OH in a concentration dependent manner. CONCLUSION The results indicate that tea polyphenol could protect the injury on cerebral ischemia reperfusion in rats for OFR, these effects may be related to its scavenging effects on oxygen free radicals and antilipid peroxidant.
文摘The effect of weak light on the peroxidation of membrane_lipid of one_year_old cherries ( Prunus pseudocerasus L. 'Laiyang') was studied by whole_tree shading. The results showed that the net photosynthetic rate of cherry leaves under weak light was remarkably lower; the activity peroxidase (POD) increased when light intensity decreased; the activity of catalase (CAT) showed an opposite trend, and it was positively correlated with light intensity; the activity of superoxide dismutase (SOD) increased under 366 μmol·m -2 ·s -1 and 533.8 μmol·m -2 ·s -1 light intensity, but decreased under 228.8 μmol·m -2 ·s -1 and 83.9 μmol·m -2 ·s -1 light intensity. A remarkable increase of malondialdehyde (MDA), a product of membrane_lipid peroxidation, was also observed in cherry leaves when treated with weak light, indicating more serious peroxidation in the membrane.
文摘Relationships between fluorescence parameters and membrane lipid peroxidation in leaves of indica and japonica rice (Oryza sativa L.) during later growth stage were studied under chilling temperature and strong light stress conditions. Results showed that D1 protein contents of PSⅡ in photosynthetic apparatus dropped, the generation of antheraxanthin (A) and zeaxanthin (Z) of xanthophyll cycle were inhibited partly, PSⅡ photochemical efficiency (F v/F m)and non-photochemical quenching (q N) were also decreased obviously. In addition, endogenous active oxygen scavenger—superoxide dismutase (SOD) reduced, superoxide anion radical (O -· 2) and malondialdehyde (MDA) accumulated, as a result, photooxidation of leaves occurred under chilling temperature and strong light stress conditions. Obvious differences in the changes of the above mentioned physiological parameters between indica and japonica rice were observed. Experiments in leaves treated with inhibitors under chilling temperature and strong light conditions showed that indica rice was more sensitive to chilling temperature with strong light and subjected to photooxidation more than japonica rice. Notable positive correlation between D1 protein contents and F v/F m or (A+Z)/(A+Z+V), and a marked negative correlation between F v/F m and MDA contents were obtained by regression analysis in indica and japonica rice during chilling temperature and strong light conditions. According to the facts mentioned above, it was inferred that PSⅡ photochemical efficiency(F v/F m) was the key index to forecast for the prediction of photooxidation under stress circumstances and the physiological basis were the synthetic capacity of D1 protein and the protection of xanthophyll cycle.
文摘Using various high-yield rices (Oryza sativa L.) such as japonica cultivar 9516, two parental line hybrid rice between subspecies with more japonica element Peiai 64/E32, Liangyoupeijiu (Peiai 64/9311), and indica hybrid rices X07S/Zihui 100, Gangyou 881, Shanyou 63 as the materials, the characteristics of chlorophyll fluorescence and membrane-lipid peroxidation of detached leaves at booting stage under photooxidation conditions were studied. In comparison with indica hybrid rice, after the photooxidation treatment, the primary photochemical efficiency of PS II (F-v/F-m), quantum yield of linear electron transport of PS II (Phi(PSII)) and photochemical quenching coefficient (qP) in japonica cultivar and hybrid rice with japonica decreased less. This indicated that high-yield rice with japonica was able to maintain higher capability of light energy conversion, resulting in the alleviation of photoinhibition. Meanwhile, the higher activities of protective enzymes such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) led to the less accumulation of endogenous active oxygen (O-(2)(radical anion), H2O2) and less content of the malondialdehyde (MDA) and the less decline of chlorophyll and protein contents, indicating a stronger tolerance to photooxidation. The changes in contents of chlorophyll and protein among various nee cultivars during photooxidation treatment were consistent with the decline of chlorophyll content from heading stage to maturation stage under natural conditions. Statistical analysis showed that there was a significant correlation between the indexes of tolerance to photooxidation and the rate of seed setting, implying that the cultivar tolerated to photooxidation had higher resistance to early aging of leaf. These results suggested that from a view of superhigh-yield breeding, considering both the utilization of heterosis and the resistance to early aging of leaf, introduction of japonica element tolerating to photooxidation into the rice sterile line (maternal plant) is a breeding strategy worthy to pay great attention to.
