FOXO1 and LXRα downregulate the apolipoprotein A-I gene expression during hydrogen peroxide-induced oxidative stress in HepG2 cells

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• 作者：Vladimir S. Shavva ; Alexandra M. Bogomolova…
• 关键词：Apolipoprotein A ; I ; Oxidative stress ; Hydrogen peroxide ; FOXO1 ; LXRα
• 刊名：Cell Stress and Chaperones
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：22
• 期：1
• 页码：123-134
• 全文大小：
• 刊物主题：Biomedicine, general; Cell Biology; Biochemistry, general; Immunology; Cancer Research; Neurosciences;
• 出版者：Springer Netherlands
• ISSN：1466-1268
• 卷排序：22

文摘

Reactive oxygen species damage various cell components including DNA, proteins, and lipids, and these impairments could be a reason for severe human diseases including atherosclerosis. Forkhead box O1 (FOXO1), an important metabolic transcription factor, upregulates antioxidant and proapoptotic genes during oxidative stress. Apolipoprotein A-I (ApoA-I) forms high density lipoprotein (HDL) particles that are responsible for cholesterol transfer from peripheral tissues to liver for removal in bile in vertebrates. The main sources for plasma ApoA-I in mammals are liver and jejunum. Hepatic apoA-I transcription depends on a multitude of metabolic transcription factors. We demonstrate that ApoA-I synthesis and secretion are decreased during H₂O₂-induced oxidative stress in human hepatoma cell line HepG2. Here, we first show that FOXO1 binds to site B of apoA-I hepatic enhancer and downregulates apoA-I gene activity in HepG2 cells. Moreover, FOXO1 and LXRα transcription factors participate in H₂O₂-triggered downregulation of apoA-I gene together with Src, JNK, p38, and AMPK kinase cascades. Mutations of sites B or C as well as the administration of siRNAs against FOXO1 or LXRα to HepG2 cells abolished the hydrogen peroxide-mediated suppression of apoA-I gene.