Sirt3的过表达通过线粒体异柠檬酸脱氢酶2（IDH2）去乙酰化抑制巨噬细胞中的脂质积累。
Overexpression of Sirt3 inhibits lipid accumulation in macrophages through mitochondrial IDH2 deacetylation.
作者信息
Sheng Shangchun, Kang Yi, Guo Yongchan, Pu Qinli, Cai Miao, Tu Zhiguang
机构信息
The Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University Chongqing, China.
The Molecular Diagnosis Laboratory of No. 2 People's Hospital of Yibin Yibin, China.
出版信息
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9196-201. eCollection 2015.
Abstract
This study aims to explore the relationship between Sirt3 expression and lipid accumulation in macrophages by inducing mitochondrial IDH2 deacetylation. In this study, Sirt3 interference and overexpression lentiviral vectors were constructed. Macrophages collected from C57BL/6J mice by peritoneal lavage were used to construct Sirt3 gene interference and overexpression models, and cultured in medium containing 1 mg/ml ox-LDL for 72 h to observe the enrichment of ox-LDL. Reverse transcription PCR was used to detect the expression of Sirt3 mRNA, western blot to detect Sirt3 and acetylated IDH2 proteins, and Nile Red staining and flow cytometry to detect intracellular lipids in macrophages. The results indicated that as compared to Sirt3 overexpressed and normal groups, the acetylation of IDH2 and accumulation of ox-LDL were significantly higher in the Sirt3 inhibited group. In conclusion, the expression of Sirt3 can inhibit lipid accumulation in macrophages by inducing mitochondrial IDH2 deacetylation.
摘要
本研究旨在通过诱导线粒体异柠檬酸脱氢酶2（IDH2）去乙酰化来探索沉默调节蛋白3（Sirt3）表达与巨噬细胞脂质蓄积之间的关系。在本研究中，构建了Sirt3干扰和过表达慢病毒载体。通过腹腔灌洗从C57BL/6J小鼠收集巨噬细胞，用于构建Sirt3基因干扰和过表达模型，并在含有1 mg/ml氧化型低密度脂蛋白（ox-LDL）的培养基中培养72小时，以观察ox-LDL的富集情况。采用逆转录聚合酶链反应（RT-PCR）检测Sirt3 mRNA的表达，蛋白质免疫印迹法检测Sirt3和乙酰化IDH2蛋白，尼罗红染色和流式细胞术检测巨噬细胞内脂质。结果表明，与Sirt3过表达组和正常组相比，Sirt3抑制组中IDH2的乙酰化和ox-LDL的蓄积显著更高。总之，Sirt3的表达可通过诱导线粒体IDH2去乙酰化来抑制巨噬细胞中的脂质蓄积。
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本文引用的文献
1
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Mol Med Rep. 2015 May;11(5):3715-21. doi: 10.3892/mmr.2015.3187. Epub 2015 Jan 13.
2
Enhancement of interaction of BSEP and HAX-1 on the canalicular membrane of hepatocytes in a mouse model of cholesterol cholelithiasis.在胆固醇性胆结石小鼠模型中，增强肝细胞胆小管膜上BSEP与HAX-1的相互作用。
Int J Clin Exp Pathol. 2014 Mar 15;7(4):1644-50. eCollection 2014.
3
Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apo)A-I from murine RAW 264.7 macrophages.线粒体功能参与调节鼠源 RAW 264.7 巨噬细胞内胆固醇向载脂蛋白 A-I（apoA-I）的外排。
Lipids Health Dis. 2012 Dec 10;11:169. doi: 10.1186/1476-511X-11-169.
4
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Exp Gerontol. 2013 Jul;48(7):634-9. doi: 10.1016/j.exger.2012.08.007. Epub 2012 Aug 31.
5
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6
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J Clin Invest. 2010 Aug;120(8):2817-28. doi: 10.1172/JCI42020. Epub 2010 Jul 19.
7
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Science. 2010 Feb 19;327(5968):1000-4. doi: 10.1126/science.1179689.
8
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Cardiovasc Res. 2010 Jun 1;86(3):526-34. doi: 10.1093/cvr/cvq015. Epub 2010 Jan 18.
9
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Anal Biochem. 2009 Nov 1;394(1):101-9. doi: 10.1016/j.ab.2009.07.019. Epub 2009 Jul 16.
10
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J Mol Biol. 2008 Oct 10;382(3):790-801. doi: 10.1016/j.jmb.2008.07.048. Epub 2008 Jul 25.
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