AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-...AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aido-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rvl cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family I member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form π-π interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family I member C3 enzyme activity and the inhibition of 22Rvl prostate cancer cell growth by decreasing the intfacellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKRlC3 inhibitors using berberine as the lead compound.展开更多
The red-orange emitting phosphor YBO3：Eu3＋was prepared by aldo-keto method and solid state diffusion. Aldo-keto method implied to decrease the processing time and heating temperature. The red-orange emitting phospho...The red-orange emitting phosphor YBO3：Eu3＋was prepared by aldo-keto method and solid state diffusion. Aldo-keto method implied to decrease the processing time and heating temperature. The red-orange emitting phosphor was characterized by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, as well as emission and excitation photoluminescence spectra re-corded at room temperature. The result of aldo-keto method showed that the phosphor YBO3：Eu3＋could be obtained at 900 °C in less time^60%as compared to solid state diffusion （SSD）. The material showed that the strongest emission peak at 595 nm under excitation at 233 nm was only due to forced magnetic dipole 5D0→7F1 transition of Eu3＋ions. Significantly, the emission inten-sity of YBO3：Eu3＋phosphor prepared by aldo-keto method was relatively higher as compared to that obtained by the solid state diffusion.展开更多
Foxtail millet (Setaria italica L.) is a drought-tolerant millet crop of arid and semi-arid regions. Aldo-keto reductases (AKRs) are significant part of plant defence mechanism, having an ability to confer multiple st...Foxtail millet (Setaria italica L.) is a drought-tolerant millet crop of arid and semi-arid regions. Aldo-keto reductases (AKRs) are significant part of plant defence mechanism, having an ability to confer multiple stress tolerance. In this study, AKR1 gene expression was studied in roots and leaves of foxtail millet subjected to different regimes of PEG- and NaCl-stress for seven days. The quantitative Real-time PCR expression analysis in both root and leaves showed upregulation of AKR1 gene during PEG and salt stress. A close correlation exits between expression of AKR1 gene and the rate of lipid peroxidation along with the retardation of growth. Tissue-specific differences were found in the AKR1 gene expression to the stress intensities studied. The reduction in root and shoot growth under both stress conditions were dependent on stress severity. The level of lipid peroxidation as indicated by MDA formation was significantly increased in roots and leaves along with increased stress levels. Finally, these findings support the early responsive nature of AKR1 gene and seem to be associated at least in part with its ability to contribute in antioxidant defence related pathways which could provide a better protection against oxidative stress under stress conditions.展开更多
Objective To determine whether extraadrenal tissues synthesize aldoster one in addition to vascular tissue and brain. Methods Ex vivo kidney perfusion was performed in normal Wistar rats, A CEI pretreated and adrena...Objective To determine whether extraadrenal tissues synthesize aldoster one in addition to vascular tissue and brain. Methods Ex vivo kidney perfusion was performed in normal Wistar rats, A CEI pretreated and adrenalectomized rats prior to the perfusion experiment. Afte r equilibration for 30 minutes, 120 ml of perfusate was collected and subjected to rever se phase HPLC and then aldosterone was measured by RIA. By RT PCR and Southern blot the expression of aldosterone synthase gene CYP11B2 mRNA was studied i n both kidney tissue and cultured renal tubular epithelial cell, lung and l iver tissues. In situ hybridization was used to identify the cell types of liver and lung expressing CYP11B2 mRNA.Results Production of aldosterone in the kidney perfusate was not chang ed in adrenalectomized rats although it was decreased in the group pretreated wi th ACEI perindopril. By RT PCR and Southern blot the expression of CYP11B2 mRNA was demonstrated in both kidney tissue and cultured renal tubular epithelial cell. We have also identified CYP11B2 mRNA expression in liver and lung of rats. In si tu hybridization showed that CYP11B2 mRNA was localized in the endoplasm of live r fat storing cell (Ito cells) and type Ⅱ alveolar cells of lung.Conclusions These studies prove that kidney, liver and lung are able to produce aldosterone.展开更多
The involvement of aldo-keto reductases （AKRs） in tumorigenesis is widely reported, but their roles in the pathological process are not generally recognized due to inconsistent measure- ments of their expression. To...The involvement of aldo-keto reductases （AKRs） in tumorigenesis is widely reported, but their roles in the pathological process are not generally recognized due to inconsistent measure- ments of their expression. To overcome this problem, we simultaneously employed real-time PCR to examine gene expression and multiple reaction monitoring （MRM） of mass spectrometry （MS） to examine the protein expression of AKRs in five different hepatic cell lines. These include one rela- tively normal hepatic cell line, L-02, and four hepatocellular carcinoma （HCC） cell lines, HepG2, HUH7, BEL7402 and SMMC7721. The results of real-time PCR showed that expression of genes encoding the AKR1C family members rather than AKR1A and AKR1B was associated with tumor, and most of genes encoding AKRs were highly expressed in HUH7. Similar observations were obtained through MRM. Different from HUH7, the protein abundance of AKR1A and AKR1B was relatively consistent among the other four hepatic cell lines, while protein expression of AKR1C varied significantly compared to L-02. Therefore, we conclude that the abundant distri- bution of AKR 1C proteins is likely to be associated with liver tumorigenesis, and the AKR expres- sion status in HuH7 is completely different from other liver cancer cell lines. This study, for the first time, provided both overall and quantitative information regarding the expression of AKRs at both mRNA and protein levels in hepatic cell lines. Our observations put the previous use of AKRs as a biomarker into question since it is only consistent with our data from HUH7. Furthermore, the data presented herein demonstrated that quantitative evaluation and comparisons within a protein fam- ily at both mRNA and protein levels were feasible using current techniques.展开更多
Ethyl(R)-4-chloro-3-hydroxybutyrate((R)-CHBE),as a chiral intermediate,is widely used in the synthesis of various chiral drugs.In this study,we screened two aldo–keto reductases(LP-AKRs)from the probiotic Lactobacill...Ethyl(R)-4-chloro-3-hydroxybutyrate((R)-CHBE),as a chiral intermediate,is widely used in the synthesis of various chiral drugs.In this study,we screened two aldo–keto reductases(LP-AKRs)from the probiotic Lactobacillus plantarum DSM20174,both with a molecular weight of approximately 31 kDa.Both enzymes could reduce 4-chloroacetoacetic acid ethyl ester(COBE)to produce(R)-CHBE with an enantioselectivity value of 99%.When determining the kinetic parameter,the K_(m),K_(cat),and V_(max)of LP-AKR5 and LP-AKR9 were 9.5 mM,7.6 U/mg,3.96 s^(-1)and 8.7 mM,8.59 U/mg,4.47 s^(-1),respectively.Both LP-AKR5 and LP-AKR9 had an optimal reaction pH of 6 and could maintain a high level of stability at pH 6,allowing them to perform well in an acidic environment.LP-AKR5 and LP-AKR9 had optimal reaction temperatures of 30℃and 40℃,respectively.Metal ions had minimal influence on LP-AKR5 and LP-AKR9 enzyme activities.This series of enzymatic properties showed that LP-AKR5 and LP-AKR9 mined from Lactobacillus plantarum DSM20174 could asym-metrically catalyze the synthesis of(R)-CHBE under weakly acidic circumstances,which could maintain product stability and provide a good foundation for industrial production.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （81302206 and 81560422）, the Development and Reform Commission of Jilin Province （2013C026-2）, and the Young Scholars Program of Norman Bethune Health Science Center of Jilin University （2013201012）, the Health and Family Planning Commission of Jiangxi Province （20143207） and the Natural Science Foundation of Jiangxi Province of China （20151BAB205016 and 20132BAB205008）.
文摘AIdo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aido-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rvl cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family I member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form π-π interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family I member C3 enzyme activity and the inhibition of 22Rvl prostate cancer cell growth by decreasing the intfacellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKRlC3 inhibitors using berberine as the lead compound.
文摘The red-orange emitting phosphor YBO3：Eu3＋was prepared by aldo-keto method and solid state diffusion. Aldo-keto method implied to decrease the processing time and heating temperature. The red-orange emitting phosphor was characterized by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, as well as emission and excitation photoluminescence spectra re-corded at room temperature. The result of aldo-keto method showed that the phosphor YBO3：Eu3＋could be obtained at 900 °C in less time^60%as compared to solid state diffusion （SSD）. The material showed that the strongest emission peak at 595 nm under excitation at 233 nm was only due to forced magnetic dipole 5D0→7F1 transition of Eu3＋ions. Significantly, the emission inten-sity of YBO3：Eu3＋phosphor prepared by aldo-keto method was relatively higher as compared to that obtained by the solid state diffusion.
文摘Foxtail millet (Setaria italica L.) is a drought-tolerant millet crop of arid and semi-arid regions. Aldo-keto reductases (AKRs) are significant part of plant defence mechanism, having an ability to confer multiple stress tolerance. In this study, AKR1 gene expression was studied in roots and leaves of foxtail millet subjected to different regimes of PEG- and NaCl-stress for seven days. The quantitative Real-time PCR expression analysis in both root and leaves showed upregulation of AKR1 gene during PEG and salt stress. A close correlation exits between expression of AKR1 gene and the rate of lipid peroxidation along with the retardation of growth. Tissue-specific differences were found in the AKR1 gene expression to the stress intensities studied. The reduction in root and shoot growth under both stress conditions were dependent on stress severity. The level of lipid peroxidation as indicated by MDA formation was significantly increased in roots and leaves along with increased stress levels. Finally, these findings support the early responsive nature of AKR1 gene and seem to be associated at least in part with its ability to contribute in antioxidant defence related pathways which could provide a better protection against oxidative stress under stress conditions.
文摘Objective To determine whether extraadrenal tissues synthesize aldoster one in addition to vascular tissue and brain. Methods Ex vivo kidney perfusion was performed in normal Wistar rats, A CEI pretreated and adrenalectomized rats prior to the perfusion experiment. Afte r equilibration for 30 minutes, 120 ml of perfusate was collected and subjected to rever se phase HPLC and then aldosterone was measured by RIA. By RT PCR and Southern blot the expression of aldosterone synthase gene CYP11B2 mRNA was studied i n both kidney tissue and cultured renal tubular epithelial cell, lung and l iver tissues. In situ hybridization was used to identify the cell types of liver and lung expressing CYP11B2 mRNA.Results Production of aldosterone in the kidney perfusate was not chang ed in adrenalectomized rats although it was decreased in the group pretreated wi th ACEI perindopril. By RT PCR and Southern blot the expression of CYP11B2 mRNA was demonstrated in both kidney tissue and cultured renal tubular epithelial cell. We have also identified CYP11B2 mRNA expression in liver and lung of rats. In si tu hybridization showed that CYP11B2 mRNA was localized in the endoplasm of live r fat storing cell (Ito cells) and type Ⅱ alveolar cells of lung.Conclusions These studies prove that kidney, liver and lung are able to produce aldosterone.
基金the National High-tech R&D Program of China(Grant No.2012AA020206)
文摘The involvement of aldo-keto reductases （AKRs） in tumorigenesis is widely reported, but their roles in the pathological process are not generally recognized due to inconsistent measure- ments of their expression. To overcome this problem, we simultaneously employed real-time PCR to examine gene expression and multiple reaction monitoring （MRM） of mass spectrometry （MS） to examine the protein expression of AKRs in five different hepatic cell lines. These include one rela- tively normal hepatic cell line, L-02, and four hepatocellular carcinoma （HCC） cell lines, HepG2, HUH7, BEL7402 and SMMC7721. The results of real-time PCR showed that expression of genes encoding the AKR1C family members rather than AKR1A and AKR1B was associated with tumor, and most of genes encoding AKRs were highly expressed in HUH7. Similar observations were obtained through MRM. Different from HUH7, the protein abundance of AKR1A and AKR1B was relatively consistent among the other four hepatic cell lines, while protein expression of AKR1C varied significantly compared to L-02. Therefore, we conclude that the abundant distri- bution of AKR 1C proteins is likely to be associated with liver tumorigenesis, and the AKR expres- sion status in HuH7 is completely different from other liver cancer cell lines. This study, for the first time, provided both overall and quantitative information regarding the expression of AKRs at both mRNA and protein levels in hepatic cell lines. Our observations put the previous use of AKRs as a biomarker into question since it is only consistent with our data from HUH7. Furthermore, the data presented herein demonstrated that quantitative evaluation and comparisons within a protein fam- ily at both mRNA and protein levels were feasible using current techniques.
文摘Ethyl(R)-4-chloro-3-hydroxybutyrate((R)-CHBE),as a chiral intermediate,is widely used in the synthesis of various chiral drugs.In this study,we screened two aldo–keto reductases(LP-AKRs)from the probiotic Lactobacillus plantarum DSM20174,both with a molecular weight of approximately 31 kDa.Both enzymes could reduce 4-chloroacetoacetic acid ethyl ester(COBE)to produce(R)-CHBE with an enantioselectivity value of 99%.When determining the kinetic parameter,the K_(m),K_(cat),and V_(max)of LP-AKR5 and LP-AKR9 were 9.5 mM,7.6 U/mg,3.96 s^(-1)and 8.7 mM,8.59 U/mg,4.47 s^(-1),respectively.Both LP-AKR5 and LP-AKR9 had an optimal reaction pH of 6 and could maintain a high level of stability at pH 6,allowing them to perform well in an acidic environment.LP-AKR5 and LP-AKR9 had optimal reaction temperatures of 30℃and 40℃,respectively.Metal ions had minimal influence on LP-AKR5 and LP-AKR9 enzyme activities.This series of enzymatic properties showed that LP-AKR5 and LP-AKR9 mined from Lactobacillus plantarum DSM20174 could asym-metrically catalyze the synthesis of(R)-CHBE under weakly acidic circumstances,which could maintain product stability and provide a good foundation for industrial production.
