Sirt1抑制内质网依赖的巨噬细胞凋亡-现代医学

Sirt1抑制内质网依赖的巨噬细胞凋亡

单位：上海健康医学院附属第六人民医院东院心内科, 上海 201306

分类号：R34

出版年·卷·期（页码）：2017·36·第八期（1059-1064）

摘要：

目的：探讨Sirt1在内质网应激诱导巨噬细胞凋亡中的作用。方法：用衣霉素、白藜芦醇、尼克酰胺干预巨噬细胞后，应用Western blot检测Sirt1、内质网应激标志物GRP78、CHOP的活性，应用流式细胞仪检测巨噬细胞凋亡。结果：衣霉素诱发了巨噬细胞内质网应激，GRP78、CHOP以及细胞凋亡明显高于对照组（P<0.05），同时激活了Sirt1，与对照组相比P<0.05；应用衣霉素干预巨噬细胞同时，加用Sirt1激活剂白藜芦醇，与单用衣霉素组相比，Sirt1明显增高（P<0.05），GRP78、CHOP以及细胞凋亡明显减少（P<0.05）；应用衣霉素干预巨噬细胞同时，加用Sirt1抑制剂尼克酰胺，与单用衣霉素组相比，Sirt1明显减少（P<0.05），GRP78、CHOP以及细胞凋亡明显增加（P<0.05）。结论：Sirt1可以保护内质网应激诱导的巨噬细胞凋亡。

Objective: To investigate the role of Sirt1 in the apoptosis of macrophage induced by endoplasmic reticulum stress.Methods: After macrophage treated with tunicamycin, resveratrol and nicotinamide, Sirt1, endoplasmic reticulum stress markers GRP78 and CHOP were detected usingh Western blot, the apoptosis of macrophage was tested by flow cytometry. Results: The tunicamycin induced macrophage endoplasmic reticulum stress.GRP78, CHOP and apoptosis in the group treated with tunicamycin were significantly higher than those in the control group(P<0.05), and Sirt1 was activated at the same time compared with the control group(P<0.05).When treated with bothtunicamycin and Sirt1 activator resveratrol, GRP78, CHOP and apoptosis were significantly decreased(P<0.05), and Sirt1 was significantly increased(P<0.05) compared with the single tunicamycin group. Sirt1 decreased significantly(P<0.05), GRP78, CHOP and cells apoptosis were significantly increased(P<0.05) when treated with bothtunicamycin and Sirt1 inhibitor nicotinamide.Conclusion: Sirt1 can protect endoplasmic reticulum stress-induced apoptosis of macrophages.

参考文献：

[1] CONG G,YAN R,HUANG H,et al.Involvement of histonemethylation in macrophageapoptosis and unstableplaqueformation in methionine-induced hyperhomocysteinemic ApoE-/-mice[J].Life Sci,2017,(173):135-144.
[2] FRYE R A.Phylogeneticclassification of prokaryotic and eukaryotic Sir2-likeproteins[J].Biochem Biophys Res Commun,2000,273(2):793-798.
[3] LAWSON M,UCIECHOWSKA U,SCHEMIES J,et al.Inhibitors to understand molecular mechanisms of NAD(+)-dependent deacetylases(sirtuins)[J].Biochim Biophys Acta,2010,1799(10-12):726-739.
[4] SUNDARESAN N R,PILLAI V B,GUPTA M P.Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy[J].J Mol Cell Cardiol,2011,51(4):614-618.
[5] DING M,LEI J,HAN H,et al.SIRT1protects against myocardial ischemia-reperfusion injury via activating eNOS in diabeticrats[J].Cardiovasc Diabetol,2015,14(1):143.
[6] AKKAFA F,ALTIPARMAK I H,ERKUS M E,et al.OP-144 attenuated reduced SIRT1 expression correlates with enhanced oxidative stress in compensated and decompensated heart failure[J].Redox Biol,2015,115(supplement1):169-173.
[7] NADTOCHIY S M,URCIUOLI W,ZHANG J,et al.Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation[J].J Mol Cell Cardiol,2015,(88):64-72.
[8] BOYCE M,YUAN J.Cellular response to endoplasmic reticulum stress:a matter of life or death[J].Cell Death Differ,2006,13(3):363-373.
[9] TABAS I.The role of endoplasmic reticulum stress in the progression of atherosclerosis[J].Circ Res,2010,107(7):839-850.
[10] YAO S,TIAN H,ZHAO L,et al.Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway[J].J Lipid Res,2017,58(1):164-177.
[11] ZHANG Q J,WANG Z,CHEN H Z,et al.Endothelium-specific overexpression of class Ⅲ deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice[J].Cardiovasc Res,2008,80(2):191-199.
[12] STEIN S,LOHMANN C,SCHA··FER N,HOFMANN J,et al.SIRT1decreases Lox-1-mediated foam cell formation in atherogenesis[J].Eur Heart J,2010,31(18):2301-2309.

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