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烟酰胺核糖通过Sirt3-PGC-1α通路改善成年小鼠心肌细胞缺氧/复氧损伤(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第2期
页码:
129-133
栏目:
基础研究
出版日期:
2016-11-25

文章信息/Info

Title:
Nicotinamide riboside alleviates hypoxia/reoxygenation injury in adult mouse cardiomyocytes via Sirt3-PGC-1α pathway
作者:
吕 平; 胡建华; 纪兆乐; 杨亚丽; 吴 萌; 尹志勇; 李 妍
（第四军医大学西京医院心血管内科，陕西 西安 710032）
Author(s):
L? Ping;  HU Jian-hua;  JI Zhao-le;  YANG Ya-li;  WU Meng;  YIN Zhi-yong;  LI Yan
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
成年小鼠心肌细胞; 烟酰胺核糖; 线粒体合成; 缺氧/复氧损伤; 过氧化物酶体增生物活化受体助激活剂-1α
Keywords:
adult mouse cardiomyocytes;  nicotinamide riboside;  mitochondrial biogenesis;  hypoxia/ reoxygenation injury;  peroxisome proliferator-activated receptor co-activator 1 alpha
分类号:
R392.2
DOI:
-
文献标识码:
A
摘要:
目的 明确烟酰胺核糖（Nicotinamide riboside，NR）对成年小鼠心肌细胞在缺氧/复氧(Hypoxia/Reoxygenation,H/R)条件下线粒体合成的影响及其潜在机制。方法 分离成年小鼠心肌细胞后，将细胞分为①对照组；②H/R组；③H/R加NR组；④H/R加NR加过氧化物酶体增生物活化受体助激活剂(Peroxisome proliferator-activated receptor co-activator alpha,PGC)-1α小干扰RNA组(H/R+NR+PGC-1α siRNA组)。TUNEL法、流式细胞术检测凋亡，JC-1染色检测线粒体膜电位，Western blot法检测线粒体合成相关蛋白PGC-1α、核呼吸因子(Nuclear respiratory factor,NRF)1和线粒体转录因子A(Mitochondrial transcription factor A,Tfam)的蛋白表达水平。结果 与对照组相比，H/R干预后，细胞凋亡增加，线粒体膜电位降低，PGC-1α、NRF1和Tfam表达降低，加入NR后，细胞凋亡减少，线粒体膜电位增高，PGC-1α、NRF1和Tfam的蛋白表达增高，然而，干扰PGC-1α后，NR的作用减弱。结论 烟酰胺核糖通过提高PGC-1α表达水平改善线粒体合成，最终减轻成年小鼠心肌细胞H/R损伤。
Abstract:
AIM To investigate the role of nicotinamide riboside (NR) in mitochondrial biogenesis in adult mouse cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. METHODS Adult mouse cardiomyocytes were divided into four groups randomly with or without 50 μmol/L nicotinamide riboside for 48 h. After hypoxia/reoxygenation (4 h/4 h), cell apoptosis was detected by TUNEL and flow cytometry, whereas mitochondrial membrane potential was assessed by JC-1. Protein expressions of peroxisome proliferator-activated receptor co-activator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam) were analyzed by Western blot. RESULTS Compared with those in the control group, H/R significantly increased the cell apoptosis index and reduced the mitochondrial membrane potential as well as the expression of PGC-1α, NRF1 and Tfam. However, NR decreased the cell apoptosis index and improved the mitochondrial membrane potential as well as the expression of PGC-1α, NRF1 and Tfam, which were reversed after knockdown of PGC-1α by siRNA. CONCLUSION Nicotinamide riboside, as a potential treatment, could improve mitochondrial biogenesis via up-regulating the expression of PGC-1α, which could eventually reduce hypoxia/reoxygenation injury in adult mouse cardiomyocytes.

参考文献/References

[1]Brenmoehl J,Hoeflich A.Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3[J].Mitochondrion,2013,13(6):755-761.
[2]Jornayvaz FR,Shulman GI.Regulation of mitochondrial biogenesis[J].Essays Biochem,2010,47:69-84.
[3]Karamanlidis G,Nascimben L,Couper GS,et al.Defective DNA replication impairs mitochondrial biogenesis in human failing hearts[J].Circ Res,2010,106(9):1541-1548.
[4]Bieganowski P,Brenner C.Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans[J].Cell,2004,117(4):495-502.
[5]Chi Y,Sauve AA.Nicotinamide riboside,a trace nutrient in foods,is a Vitamin B3 with effects on energy metabolism and neuroprotection[J].Curr Opin Clin Nutr Metab Care,2013,16(6):657-661.
[6]Dagon Y,Avraham Y,Magen I,et al.Nutritional status,cognition,and survival:a new role for leptin and AMP kinase[J].J Biol Chem,2005,280(51):42142-42148.
[7]Graham EL,Balla C,Franchino H,et al.Isolation, culture, and functional characterization of adult mouse cardiomyoctyes[J].J Vis Exp,2013(79):e50289.
[8]Ren J,Pulakat L,Whaley-Connell A,et al.Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease[J].J Mol Med(Berl), 2010,88(10):993-1001.
[9]Gottlieb RA,Gustafsson SB.Mitochondrial turnover in the heart[J].Biochim Biophys Acta,2011,1813(7):1295-1301.
[10]Scarpulla RC.Transcriptional paradigms in mammalian mitochondrial biogenesis and function[J].Physiol Rev,2008,88(2):611-638.
[11]Sun L,Zhao M,Yu X,et al.Cardioprotection by acetylcholine:A novel mechanism via mitochondrial biogenesis and function involving the PGC-1α pathway[J].J Cell Physiol,2013,228(6):1238-1248.
[12]Bogan KL,Brenner C.Nicotinic acid,nicotinamide,and nicotinamide riboside:a molecular evaluation of NAD+ precursor vitamins in human nutrition[J].Annu Rev Nutr,2008,28:115-130.
[13]Gong B,Pan Y,Vempati P,et al.Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-gamma coactivator 1alpha regulated beta-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models[J].Neurobiol Aging,2013,34(6):1581-1588.
[14]Khan NA,Auranen M,Paetau I,et al.Effective treatment of mitochondrial myopathy by nicotinamide riboside,a vitamin B3[J].EMBO Mol Med,2014,6(6):721-731.
[15]Cantó C,Houtkooper RH,Pirinen E,et al.The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity[J].Cell Metabolism,2012,15(6):838-847.
[16]Brown KD,Maqsood S,Huang JY,et al.Activation of SIRT3 by the NAD(+) precursor nicotinamide riboside protects from noise-induced hearing loss[J].Cell Metab,2014,20(6):1059-1068.
[17]Tseng AHH,Shieh S,Wang DL.SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage[J].Free Radic Biol Med,2013,63:222-234.
[18]Palacios OM,Carmona JJ,Michan S,et al.Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle[J].Aging(Albany NY),2009,1(9):771-783.

备注/Memo

备注/Memo:
收稿日期：2016-01-24.
基金项目：国家自然科学基金项目资助（81570252;81500195）
通讯作者：李妍，副教授，主要从事冠心病基础和临床研究 Email：liyanfmmu@hotmail.com
共同通讯作者：尹志勇，讲师，主要从事缺血性心脏病损伤与保护研究 Email：zhiyong_yin@163.com
作者简介：吕平，硕士生 Email：2383067104@qq.com
更新日期/Last Update: 2016-10-11