SIRT3调节脂代谢和抗氧化防御研究进展
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摘要
沉默信息调控因子2样蛋白3(SIRT3或Sirtuin3)是位于线粒体的主要去乙酰化酶,是机体脂代谢及抗氧化防御的重要调节者。SIRT3对脂肪酸β-氧化关键酶长链酰基CoA脱氢酶(LCAD)等进行脱乙酰化修饰调节脂代谢,还可活化AMPK通路调节脂代谢。SIRT3还可对抗氧化因子超氧化物歧化酶(Mn-SOD/SOD2)和异柠檬酸脱氢酶2(IDH2)的赖氨酸活化位点脱乙酰化增强抗氧化防御。论文总结SIRT3在脂代谢和抗氧化防御的调节作用,以期为揭示能量代谢障碍性疾病的发病机制提供启示,进而为探寻防治新靶标奠定理论基础。
SIRT3(silent information regulator 3),a major deacetylase in mitochondria,plays a pivotal role in the regulation of lipid metabolism and antioxidant defense.SIRT3 regulates lipid metabolism by deacetylation of long-chain acyl CoA dehydrogenase(LCAD) etc,key enzymes of fatty acid beta oxidation and also by activation of AMPK pathway.SIRT3 activates antioxidant key enzymes superoxide dismutase(Mn-SOD/SOD2) and isocitrate dehydrogenase 2(IDH2) by deacetylation of to modulate antioxidant defense.This paper systematically summarized the effect of SIRT3 in the regulation of lipid metabolism and antioxidant defense to offer new insights into the pathogenesis of common metabolic disorders further to search new target or strategy for prevention and treatment of those diseases.
SIRT3(silent information regulator 3),a major deacetylase in mitochondria,plays a pivotal role in the regulation of lipid metabolism and antioxidant defense.SIRT3 regulates lipid metabolism by deacetylation of long-chain acyl CoA dehydrogenase(LCAD) etc,key enzymes of fatty acid beta oxidation and also by activation of AMPK pathway.SIRT3 activates antioxidant key enzymes superoxide dismutase(Mn-SOD/SOD2) and isocitrate dehydrogenase 2(IDH2) by deacetylation of to modulate antioxidant defense.This paper systematically summarized the effect of SIRT3 in the regulation of lipid metabolism and antioxidant defense to offer new insights into the pathogenesis of common metabolic disorders further to search new target or strategy for prevention and treatment of those diseases.
引文
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[24] Cimen H,Han M J,Yang Y,et al.Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondrial[J].Biochemistry,2010,49(2):304-311.
[25] Ghinis-Hozumi Y,González-Gallardo A,González-Dávalos L,et al.Bovine sirtuins:initialcharacterization and expression of sirtuins 1 and 3 in liver,muscle,and adipose tissue[J].J Anim Sci,2011,89(8):2529-2536.
[2] Li S,Dou X,Ning H,et al.Sirtuin 3 acts as a negative regulatior of autophagy dictating hepatocyte susceptibility to lipotoxicity[J].Hepatology,2017,66(3):936-952.
[3] 朱林,巩会平,马艳艳,等.Srit3与心血管疾病和长寿关系的研究进展 [J].基础医学与临床,2017,37(4):553-556.
[4] 叶雪瑞,尹力,崔金金,等.SIRT3与细胞凋亡的研究进展 [J].现在生物医学进展,2017,17(13):2586-2589.
[5] Parihar P,Solanki I,Mansuri M L,et al.Mitoehondrial Sirtuins :emergingr roles in metabolicregulations,energy homeostasis and diseases[J].Exp Gerontol,2015,61:130-141.
[6] Liu P,Huang G,Wei T,et al.Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation[J].Biochim Biophys Acta,2018,1864(3):764-777.
[7] Kwon S,Seok S,Yau P,et al.Obesity and aging diminish SIRT1-mediated deacetylation of SIRT3,leading to hyperacetylation and decreased activity and stability of SIRT3[J].J Biol Chem,2017,292(42):17312-17323.
[8] Hirschey M D,Shimazu T,Jing E,et al.SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome[J].Mol Cell,2011,44(2):177-190.
[9] Borengasser S J,Lau F,Kang P,et al.Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning[J].PLoS One,2011,6(8):e24068.
[10] Grahame Hardie D.Regulation of AMP-activated protein kinase by natural and synthetic activators[J].Acta Pharm Sin B,2016,6(1):1-19.
[11] Lin J,Li D,Zhang T,et al.SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity[J].Cell Death Dis,2017,8(10):1-11.
[12] Wang Q,Liu S,Zhai A,et al.AMPK-mediated regulation of lipid metabolism by phosphorylation[J].Biol Pharm Bull,2018,41(7):985-993.
[13] Wang C,Li Y,Hao M,et al.Astragaloside IV inhibits triglyceride accumulation in insulin-resistant HepG2 cells via AMPK-induced SREBP-1c phosphorylation[J].Front Pharmacol,2018,9:345.
[14] Li X,Li X,Chen H,et al.Non-esterified fatty acids activate the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes[J].Cell Biochem Biophys,2013,67(3):1157-1169.
[15] Barreto-Torres G,Hernandez J S,Jang S,et al.The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPARα-cyclophilin D interaction in cardiomyocytes[J].Am J Physiol Heart Circ Physiol,2015,308(7):H749-758.
[16] 苏会萍,张俊强,曹威,等.MnSOD-SIRT3在佐剂性关节炎大鼠肝组织中的表达和意义[J].安徽医科大学学报,2016,51(9):1268-1272.
[17] Fu Y,Kinter M,Hudson J,et al.Aging promotes sirtuin 3-Dependent cartilage superoxide dismutase 2 acetylation and osteoarthritis[J].Arthritis Rheumatol,2016,68(8):1887-1898 .
[18] zhang J,Song X,Cao W,et a1.Autophagy and mitochondrial dysfunction in adjuvant-arthritisrats treatment with resveratrol[J].Sci Rep,2016,6:32928.
[19] Morris B J,Willcox D C,Donlon T A,et al.FOXO3:a major gene for human longevity-amini review[J].Gerontology,2015,61(6):515-525.
[20] 麦静愔,陈天阳,平键,等.MIR-384对NEFA诱导的Hepa1-6细胞sirt3/FOXO1信号通路的影响 [J].实用肝脏病杂志,2018,21(6):829-832.
[21] Mailloux R J,Beriault R,Lemire J,et al.The tricarboxylic acid cycle,an ancient metabolic network with a novel twist[J].PLoS One,2007,2(8):e690.
[22] Someya S,Yu W,Hallows W C,et al.Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction[J].Cell,2010,143(5):802-812.
[23] zhang X,Ren X,Zhang Q,et a1.PGC-Ia/ERRa-Sirt3 pathway regulates D aergic neuronal death by directly deacetylating SOD2 and ATP synthaseIS[J].Antioxid Redox Signal,2016,24(6):312-328.
[24] Cimen H,Han M J,Yang Y,et al.Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondrial[J].Biochemistry,2010,49(2):304-311.
[25] Ghinis-Hozumi Y,González-Gallardo A,González-Dávalos L,et al.Bovine sirtuins:initialcharacterization and expression of sirtuins 1 and 3 in liver,muscle,and adipose tissue[J].J Anim Sci,2011,89(8):2529-2536.