OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids

Rongsong Li, Wendy Chen, Rolando Yanes, Sangderk Lee, and Judith A. Berliner

Pathology & Lab Medicine, UCLA, Los Angeles, CA 90095

Corresponding Author: rli{at}mednet.ucla.edu

Oxidized 1-palmitoyl-2-arachidonoyl-sn-Glycero-3-phosphorylcholine (OxPAPC) is present in oxidative modified low density lipoprotein (LDL) and accumulates in the lesion of many chronic inflammatory diseases such as atherosclerosis. In a microarray study, OxPAPC has been demonstrated to modulate the expression of more than 700 genes in human aortic endothelial cells (HAEC). We found that the levels of mRNA for OKL38 (also named BDGI), a tumor growth inhibitor, were strongly increased by OxPAPC. Here we report that OKL38 is regulated by an oxidative signal induced by OxPAPC and its component lipid PEIPC. The stimulation of OKL38 by OxPAPC depends on superoxide production since NADPH oxidase (Nox) inhibitor apocynin and superoxide scavenger N-Acetyl Cysteine block the stimulation. Oxidative stress by tert-butylhydroquinone (tBHQ) treatment also induced the expression of OKL38. The stimulation of OKL38 expression by OxPAPC is mediated via transcription factor Nrf2, a common factor involved in the regulation of oxidative stress stimulated genes. Activation of Nrf2 induces the expression of OKL38 while siRNA knockdown of Nrf2 blocks the stimulation of OKL38 by OxPAPC. Our results suggest that OKL38 is regulated via NADPH Oxidase/Nrf2 pathway in response to oxidative stress stimuli.

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