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

Autor: Shavva VS; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia. shavva@iem.sp.ru.; Department of Embryology, St. Petersburg State University, St. Petersburg, Russia. shavva@iem.sp.ru., Bogomolova AM; Department of Biochemistry, St. Petersburg State University, St. Petersburg, Russia., Nikitin AA; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia.; Department of Biochemistry, St. Petersburg State University, St. Petersburg, Russia., Dizhe EB; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia., Oleinikova GN; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia., Lapikov IA; Department of Embryology, St. Petersburg State University, St. Petersburg, Russia., Tanyanskiy DA; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia.; Department of Fundamental Medicine and Medical Technologies, St. Petersburg State University, St. Petersburg, Russia., Perevozchikov AP; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia.; Department of Embryology, St. Petersburg State University, St. Petersburg, Russia., Orlov SV; Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov St., 12, St. Petersburg, 197376, Russia. serge@iem.sp.ru.; Department of Embryology, St. Petersburg State University, St. Petersburg, Russia. serge@iem.sp.ru.
Jazyk: angličtina
Zdroj: Cell stress & chaperones [Cell Stress Chaperones] 2017 Jan; Vol. 22 (1), pp. 123-134. Date of Electronic Publication: 2016 Nov 28.
DOI: 10.1007/s12192-016-0749-6
Abstrakt: 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.
Databáze: MEDLINE
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