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

Vladimir S. Shavva, Alexandra M. Bogomolova, Artemy A. Nikitin, Ella B. Dizhe, Galina N. Oleinikova, Ivan A. Lapikov, Dmitry A. Tanyanskiy, Andrej P. Perevozchikov, Sergey V. Orlov

Результат исследований: Научные публикации в периодических изданияхстатьярецензирование

11 Цитирования (Scopus)

Аннотация

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 LXR alpha 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 LXR alpha to HepG2 cells abolished the hydrogen peroxide-mediated suppression of apoA-I gene.

Язык оригиналаАнглийский
Страницы (с-по)123-134
Число страниц12
ЖурналCell Stress and Chaperones
Том22
Номер выпуска1
DOI
СостояниеОпубликовано - янв 2017

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