Hepatic overexpression of methionine sulfoxide reductase A reduces atherosclerosis in apolipoprotein E-deficient mice.

Journal of Lipid Research
Yan-Yong XuHong Yu

Abstract

Methionine sulfoxide reductase A (MsrA), a specific enzyme that converts methionine-S-sulfoxide to methionine, plays an important role in the regulation of protein function and the maintenance of redox homeostasis. In this study, we examined the impact of hepatic MsrA overexpression on lipid metabolism and atherosclerosis in apoE-deficient (apoE(-/-)) mice. In vitro study showed that in HepG2 cells, lentivirus-mediated human MsrA (hMsrA) overexpression upregulated the expression levels of several key lipoprotein-metabolism-related genes such as liver X receptor α, scavenger receptor class B type I, and ABCA1. ApoE(-/-) mice were intravenously injected with lentivirus to achieve high-level hMsrA expression predominantly in the liver. We found that hepatic hMsrA expression significantly reduced plasma VLDL/LDL levels, improved plasma superoxide dismutase, and paraoxonase-1 activities, and decreased plasma serum amyloid A level in apoE(-/-) mice fed a Western diet, by significantly altering the expression of several genes in the liver involving cholesterol selective uptake, conversion and excretion into bile, TG biosynthesis, and inflammation. Moreover, overexpression of hMsrA resulted in reduced hepatic steatosis and aortic ather...Continue Reading

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Citations

Nov 22, 2016·International Journal of Molecular Sciences·Fen DuHong Yu
Mar 30, 2018·The Journal of Biological Chemistry·Jung Mi LimRodney L Levine
Jan 13, 2018·Neurochemical Research·Jung Mi LimRodney L Levine
Jan 25, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanyong XuHong Yu
Nov 27, 2020·Journal of Cellular and Molecular Medicine·Yao WuYan Wang
Dec 29, 2019·Food Research International·Brigitte Picard, Mohammed Gagaoua
Dec 23, 2020·Antioxidants·Wenjun Wang, Peter M Kang
May 14, 2017·Atherosclerosis·Ting Ting LiuXiao Le Xu
Aug 21, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Feifei LiHong Yu

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Methods Mentioned

BETA
PCR
protein assay
transfection
transgenic

Software Mentioned

Image
Pro Plus

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