Oxidative stress induced lipid accumulation via SREBP1c activation in HepG2 cells.
SREBP1c (sterol regulatory element-binding protein 1c) is a metabolic-syndrome-associated transcription factor that controls fatty acid biosynthesis under glucose/insulin stimulation. Oxidative stress increases lipid accumulation, which promotes the generation of reactive oxygen species (ROS). However, we know little about the role of oxidative stress in fatty acid biosynthesis. To clarify the action of oxidative stress in lipid accumulation via SREBP1c, we examined SREBP1c activity in H2O2-treated mammalian cells. We introduced a luciferase reporter plasmid carrying the SREBP1c-binding site into HepG2 or COS-7 cells. With increasing H2O2 dose, SREBP1c transcriptional activity increased in HepG2 cells but declined in COS-7 cells. RT-PCR analysis revealed that mRNA expression of SREBP1c gene or of SREBP1c-regulated genes rose H2O2 dose-dependently in HepG2 cells but dropped in COS-7 cells. Lipid accumulation and levels of the nuclear form of SREBP1c increased in H2O2-stimulated HepG2 cells. ROS may stimulate lipid accumulation in HepG2 cells via SREBP1c activation.
Sekiya
Mika
M
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8572, Japan.
Hiraishi
Ako
A
Touyama
Maiko
M
Sakamoto
Kazuichi
K
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D009765:Obesity / Q000209:etiology / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D006861:Hydrogen Peroxide