Japanese Journal of Veterinary Research;Volume 58, Number 3&4

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Effects of retinoic acid and hydrogen peroxide on sterol regulatory element-binding protein-1a activation during adipogenic differentiation of 3T3-L1 cells

Eldaim, Mabrouk A. Abd;Okamatsu-Ogura, Yuko;Terao, Akira;Kimura, Kazuhiro

Permalink : http://hdl.handle.net/2115/44136
JaLCDOI : 10.14943/jjvr.58.3-4.149
KEYWORDS : adipogenesis;fatty acid synthase;H2O2;SREBP-1;vitamin A

Abstract

Both retinoic acid (RA) and oxidative stress (H2O2) increased transcription and cleavage of membrane-bound sterol regulatory element-binding protein (SREBP)-1, leading to enhanced transcription of fatty acid synthase (FAS) in hepatoma cells. On the other hand, RA and H2O2 decreased and increased lipogenesis in adipocytes, respectively, although roles of SREBP-1 activation in these effects remain to be elucidated. To elucidate its involvement, we examined the activation of SREBP-1a, expression of FAS genes and lipid accumulation in 3T3-L1 cells in the presence of RA and/or H2O2. RA (1 μM) treatment suppressed expression of SREBP-1a and FAS genes and lipid accumulation. H2O2 (2 μM) treatment induced increased cleavage of SREBP-1a, without affecting amounts of SREBP-1a mRNA and precursor protein, and enhanced expression of FAS gene and lipid accumulation. Increased cleavage of SREBP-1a by H2O2 was also observed even in the presence of RA. These results suggest that H2O2 enhances a cleavage of SREBP-1a precursor protein, which independently occurs with the RA suppression of SREBP-1a gene expression, and that RA itself has no role in the SREBP-1a activation in adipocytes.

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