Research output: Contribution to journal › Article › peer-review
FOXO1 and LXR alpha downregulate the apolipoprotein A-I gene expression during hydrogen peroxide-induced oxidative stress in HepG2 cells. / 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.
In: Cell Stress and Chaperones, Vol. 22, No. 1, 01.2017, p. 123-134.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - FOXO1 and LXR alpha downregulate the apolipoprotein A-I gene expression during hydrogen peroxide-induced oxidative stress in HepG2 cells
AU - Shavva, Vladimir S.
AU - Bogomolova, Alexandra M.
AU - Nikitin, Artemy A.
AU - Dizhe, Ella B.
AU - Oleinikova, Galina N.
AU - Lapikov, Ivan A.
AU - Tanyanskiy, Dmitry A.
AU - Perevozchikov, Andrej P.
AU - Orlov, Sergey V.
PY - 2017/1
Y1 - 2017/1
N2 - 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.
AB - 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.
KW - Apolipoprotein A-I
KW - Oxidative stress
KW - Hydrogen peroxide
KW - FOXO1
KW - LXR alpha
KW - LIVER-X RECEPTOR
KW - INSULIN-RESPONSE SEQUENCES
KW - TISSUE-SPECIFIC EXPRESSION
KW - COMPLEMENT C3 EXPRESSION
KW - HIGH-DENSITY-LIPOPROTEIN
KW - ORPHAN NUCLEAR RECEPTOR
KW - PROTEIN-KINASE B
KW - TRANSCRIPTION FACTORS
KW - TNF-ALPHA
KW - APOA-I
U2 - 10.1007/s12192-016-0749-6
DO - 10.1007/s12192-016-0749-6
M3 - статья
VL - 22
SP - 123
EP - 134
JO - Cell Stress and Chaperones
JF - Cell Stress and Chaperones
SN - 1355-8145
IS - 1
ER -
ID: 7614924