Sirtuin 3(SIRT3)is a primary mitochondrial deacetylase.Studies have confirmed that it directly activates mitophagy by modulating mitochondrial protein acetylation.As a key homeostatic mechanism,mitophagy activation al...Sirtuin 3(SIRT3)is a primary mitochondrial deacetylase.Studies have confirmed that it directly activates mitophagy by modulating mitochondrial protein acetylation.As a key homeostatic mechanism,mitophagy activation alleviates oxidative stress-induced imbalance between cell proliferation and apoptosis,corrects stress-driven mitochondrial metabolic dysfunction,and thus inhibits excessive tumor growth,exerting significant antitumor effects.These functions establish SIRT3 as a key target for regulating mitophagy and cancer therapy.Clinically,strategies centered on its precise regulation may offer a novel direction for gastric cancer(GC)prevention and treatment,with selective activation remaining a critical challenge.SIRT3 could also serve as an auxiliary indicator in clinical guidelines for assessing tumor progression.Given this potential,this minireview systematically examines SIRT3’s mechanisms in regulating mitophagy,its role in GC pathogenesis,and translational prospects for targeting SIRT3 in GC management.展开更多
Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of ...Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of GRb3 on myocardial injury induced by sleep deprivation and its mechanisms.GRb320 mg/kg group showed lower heart rate((438.20±10.06)bpm),creatine kinase((27.43±2.85)U/mg pro)and lactate dehydrogenase((412.90±35.65)U/L)than SD group((592.00±7.78)bpm,(44.18±1.24)U/mg pro,(526.60±38.18)U/L).GRb3 improved myocardial tissue damage and abnormal mitochondrial morphological changes.GRb3 also reduced the abnormal proteins expression of atrial natriuretic peptide(ANP),sirtuin 3(SIRT3),tumor protein P53(P53),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),acyl-CoA synthetase long chain family member 4(ACSL4),heme oxygenase-1(HO-1),ferritin heavy chain 1(FTH1),ferroptosis suppressor protein 1(FSP1).GRb3 ameliorated oxidative stress,such as malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).GRb3 also decreased reactive oxygen species(ROS)content,restored cellular abnormal mitochondrial morphology and reversed the expression of ferroptosis-related proteins on H9c2 cells pretreated with Erastin.While the above effect could be reversed by 3-(1H-1,2,3-triazol-4-yl)pyridine(3-TYP).In summary,GRb3 exerts cardioprotective effects by regulating SIRT3/P53/SLC7A11/GPX4 axis to inhibit myocardial ferroptosis in sleep deprived mice.The findings imply that GRb3 holds promising potential for innovative approaches to safeguarding human cardiac health.展开更多
AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 （ZEB1） was silenced...AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 （ZEB1） was silenced using a and the impact of ZEB1 and lentivirus-mediated method, methyI-CpG binding domain protein 1 （MBD1） on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 （SIRT3） expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatinimmunoprecipitation assays.RESULTS ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.CONCLUSION ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.展开更多
OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX)on renal fibrosis induced by unilateral ureteric obstruction(UUO),and on reactive oxygen species(ROS)homeostasis in human umbilical vein endotheli...OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX)on renal fibrosis induced by unilateral ureteric obstruction(UUO),and on reactive oxygen species(ROS)homeostasis in human umbilical vein endothelial cells(HUVECs).METHODS:Forty male mice were randomly divided into six groups,sham group,UUO group,UUO+resveratrol(RSV)(15 mg/kg)group,UUO+YSHX20 mg/kg group(UUO+YSHX-L),UUO+YSHX 40 mg/kg group(UUO+YSHX-M),UUO+YSHX 80 mg/kg group(UUO+YSHX-H).Western blotting was used to measure protein expression levels.Reverse transcription-quantitative polymerase chain reaction was used to measure the m RNA expression.Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample.Cell apoptosis was measured by Annexin V/PI staining.Cell viability was measured using CCK-8/WST-8 assay.RESULTS:YSHX treatment reducedα-SMA and Col-4 expressions,and increased CD31 and VE-cadherin expressions in UUO model mice.In vitro,YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions.YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor coactivator-1α(PGC-1α)/silent mating-type information regulation2 homolog 3(Sirt3)signaling.CONCLUSION:YSHX treatment reduced 109 KJ UUO-induced renal injury and fibrosis.Furthermore,YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.展开更多
文摘Sirtuin 3(SIRT3)is a primary mitochondrial deacetylase.Studies have confirmed that it directly activates mitophagy by modulating mitochondrial protein acetylation.As a key homeostatic mechanism,mitophagy activation alleviates oxidative stress-induced imbalance between cell proliferation and apoptosis,corrects stress-driven mitochondrial metabolic dysfunction,and thus inhibits excessive tumor growth,exerting significant antitumor effects.These functions establish SIRT3 as a key target for regulating mitophagy and cancer therapy.Clinically,strategies centered on its precise regulation may offer a novel direction for gastric cancer(GC)prevention and treatment,with selective activation remaining a critical challenge.SIRT3 could also serve as an auxiliary indicator in clinical guidelines for assessing tumor progression.Given this potential,this minireview systematically examines SIRT3’s mechanisms in regulating mitophagy,its role in GC pathogenesis,and translational prospects for targeting SIRT3 in GC management.
基金financially supported by the Opening Project of Shanghai Key Laboratory of Compound Chinese Medicines(21DZ2270500)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(2023YZZ02).
文摘Ginsenoside Rb3(GRb3)is an active ingredient extracted from Panax ginseng,which is known to enhance blood supply to heart and treat a variety of cardiac diseases.The aim of this study was to investigate the effect of GRb3 on myocardial injury induced by sleep deprivation and its mechanisms.GRb320 mg/kg group showed lower heart rate((438.20±10.06)bpm),creatine kinase((27.43±2.85)U/mg pro)and lactate dehydrogenase((412.90±35.65)U/L)than SD group((592.00±7.78)bpm,(44.18±1.24)U/mg pro,(526.60±38.18)U/L).GRb3 improved myocardial tissue damage and abnormal mitochondrial morphological changes.GRb3 also reduced the abnormal proteins expression of atrial natriuretic peptide(ANP),sirtuin 3(SIRT3),tumor protein P53(P53),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),acyl-CoA synthetase long chain family member 4(ACSL4),heme oxygenase-1(HO-1),ferritin heavy chain 1(FTH1),ferroptosis suppressor protein 1(FSP1).GRb3 ameliorated oxidative stress,such as malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD).GRb3 also decreased reactive oxygen species(ROS)content,restored cellular abnormal mitochondrial morphology and reversed the expression of ferroptosis-related proteins on H9c2 cells pretreated with Erastin.While the above effect could be reversed by 3-(1H-1,2,3-triazol-4-yl)pyridine(3-TYP).In summary,GRb3 exerts cardioprotective effects by regulating SIRT3/P53/SLC7A11/GPX4 axis to inhibit myocardial ferroptosis in sleep deprived mice.The findings imply that GRb3 holds promising potential for innovative approaches to safeguarding human cardiac health.
基金the National Science Fund for Distinguished Young Scholars of China,No.81625016the National Science Foundation of China,No.81502031 and No.81772555+1 种基金Shanghai Municipal Commission of Health and Family Planning Grant,No.20154Y0090Youth Research Foundation of Shanghai Municipal Commission of Health and Family Planning,No.Z0124Y074
文摘AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 （ZEB1） was silenced using a and the impact of ZEB1 and lentivirus-mediated method, methyI-CpG binding domain protein 1 （MBD1） on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 （SIRT3） expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatinimmunoprecipitation assays.RESULTS ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.CONCLUSION ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.
基金Supported by National Natural Science Foundation of China:Study on the Treatment Mechanism of"Kidney Benefiting and Blood Circulation Activation"in Renal Fibrosis Based on SIRT3 Regulation AMPK/PCG-1/CPT1A Signaling Pathways(No.81760807)Study on the Anti-renal Fibrosis Mechanism of Yishen Huoxue Formula Based on the Regulation of Hypoxia-glycolysis Pathway by Exosome Derived Mir-210(No.82060820)。
文摘OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX)on renal fibrosis induced by unilateral ureteric obstruction(UUO),and on reactive oxygen species(ROS)homeostasis in human umbilical vein endothelial cells(HUVECs).METHODS:Forty male mice were randomly divided into six groups,sham group,UUO group,UUO+resveratrol(RSV)(15 mg/kg)group,UUO+YSHX20 mg/kg group(UUO+YSHX-L),UUO+YSHX 40 mg/kg group(UUO+YSHX-M),UUO+YSHX 80 mg/kg group(UUO+YSHX-H).Western blotting was used to measure protein expression levels.Reverse transcription-quantitative polymerase chain reaction was used to measure the m RNA expression.Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample.Cell apoptosis was measured by Annexin V/PI staining.Cell viability was measured using CCK-8/WST-8 assay.RESULTS:YSHX treatment reducedα-SMA and Col-4 expressions,and increased CD31 and VE-cadherin expressions in UUO model mice.In vitro,YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions.YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor coactivator-1α(PGC-1α)/silent mating-type information regulation2 homolog 3(Sirt3)signaling.CONCLUSION:YSHX treatment reduced 109 KJ UUO-induced renal injury and fibrosis.Furthermore,YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.
