The non-coding RNA gadd7 is a regulator of lipid-induced oxidative and
endoplasmic reticulum stress.
Authors Brookheart RT, Michel CI, Listenberger LL, Ory DS, Schaffer JE
Submitted By Jean Schaffer on 3/31/2010
Status Published
Journal The Journal of biological chemistry
Year 2009
Date Published 3/20/2009
Volume : Pages 284 : 7446 - 7454
PubMed Reference 19150982
Abstract In obesity and diabetes, an imbalance in fatty acid uptake and fatty acid
utilization leads to excess accumulation of lipid in non-adipose tissues. This
lipid overload is associated with cellular dysfunction and cell death, which
contribute to organ failure, a phenomenon termed lipotoxicity. To elucidate the
molecular mechanism of lipid-mediated cell death, we generated and characterized
a mutant Chinese hamster ovary cell line that is resistant to palmitate-induced
cell death. In this mutant, random insertion of a retroviral promoter trap has
disrupted the gene for the non-coding RNA, growth arrested DNA-damage inducible
gene 7 (gadd7). Here we report that gadd7 is induced by lipotoxic stress in a
reactive oxygen species (ROS)-dependent fashion and is necessary for both lipid-
and general oxidative stress-mediated cell death. Depletion of gadd7 by
mutagenesis or short hairpin RNA knockdown significantly reduces lipid and
non-lipid induced ROS. Furthermore, depletion of gadd7 delays and diminishes
ROS-induced endoplasmic reticulum stress. Together these data are the first to
implicate a non-coding RNA in a feed-forward loop with oxidative stress and its
induction of the endoplasmic reticulum stress response.

Investigators with authorship
Jean SchafferWashington University in St Louis