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| Content Provider | Springer Nature Link |
|---|---|
| Author | Shavva, Vladimir S. Bogomolova, Alexandra M. Nikitin, Artemy A. Dizhe, Ella B. Oleinikova, Galina N. Lapikov, Ivan A. Tanyanskiy, Dmitry A. Perevozchikov, Andrej P. Orlov, Sergey V. |
| Copyright Year | 2016 |
| Abstract | 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 H$_{2}$O$_{2}$-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 H$_{2}$O$_{2}$-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. |
| Starting Page | 123 |
| Ending Page | 134 |
| Page Count | 12 |
| File Format | |
| ISSN | 13558145 |
| Journal | Cell Stress and Chaperones |
| Volume Number | 22 |
| Issue Number | 1 |
| e-ISSN | 14661268 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2016-11-28 |
| Publisher Place | Dordrecht |
| Access Restriction | Subscribed |
| Subject Keyword | Apolipoprotein A-I Oxidative stress Hydrogen peroxide FOXO1 LXRα Biomedicine Cell Biology Biochemistry Immunology Cancer Research Neurosciences |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry |
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