Fumarate and oxidative stress synergize to promote stability of C/EBP homologous protein in the adipocyte.

ABSTRACT: C/EBP homologous protein (CHOP) is a transcription factor that is elevated in adipose tissue across many models of diabetes and metabolic stress. Although increased CHOP levels are associated with the terminal response to endoplasmic reticulum stress and apoptosis, there is no evidence for CHOP mediated apoptosis in the adipose tissue during diabetes. CHOP protein levels increase in parallel with protein succination, a fumarate derived cysteine modification, in the adipocyte during metabolic stress. We investigated the factors contributing to sustained CHOP proteins levels in the adipocyte, with an emphasis on the regulation of CHOP protein turnover by metabolite-driven modification of Keap1 cysteines. CHOP protein stability was investigated in conditions of nutrient stress due to high glu

SUBMITTER: Manuel AM 

PROVIDER: S-EPMC6961135 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature