Ox-PAPC activation of PMET system increases expression of heme oxygenase-1 in human aortic endothelial cell

Journal of Lipid Research

Judith A. Berliner¹  Roland Palvolgyi¹  Qian-Zhou Yang¹  Wan Lam Szeto¹  Rongsong Li¹  Sangderk Lee²  Brandon Kim²  Tiffany Ho²  Henry Honda²  Jason Xu² 

[1] Division of Cardiology, Department of Medicine, University of California-Los Angeles, Los Angeles, CA 90095;Department of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, CA 90095;

关键词: oxidized-1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine;    plasma membrane electron transport;    Nrf2;    atherosclerosis;    endothelium;   

DOI  :  

来源: DOAJ

【 摘 要 】

Oxidized-1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine (Ox-PAPC) has been demonstrated to accumulate in atherosclerotic lesions and regulates expression of more than 1,000 genes in human aortic endothelial cell (HAEC). Among the most highly induced is heme oxygenase-1 (HO-1), a cell-protective antioxidant enzyme, which is sensitively induced by oxidative stress. To identify the pathway by which Ox-PAPC induces HO-1, we focused on the plasma membrane electron transport (PMET) complex, which contains ecto-NADH oxidase 1 (eNOX1) and NADPH:quinone oxidoreductase 1 (NQO1) and affects cellular redox status by regulating levels of NAD(P)H. We demonstrated that Ox-PAPC and its active components stimulated electron transfer through the PMET complex in HAECs from inside to outside [as determined by extracellular 2-(4-iodophenyl)-3-(44-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) reduction] and from outside to inside of the cell (as determined by intracellular NBT reduction). Chemical inhibitors of PMET system and siRNAs to PMET components (NQO1 and eNOX1) significantly decreased HO-1 induction by Ox-PAPC. We present evidence that Ox-PAPC activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in HAEC plays an important role in the induction of HO-1 and PMET inhibitors blocked Nrf2 activation by Ox-PAPC. We hypothesized that PMET activation by Ox-PAPC causes intracellular NAD(P)H depletion, which leads to the increased oxidative stress and HO-1 induction. Supporting this hypothesis, cotreatment of cells with exogenous NAD(P)H and Ox-PAPC significantly decreased oxidative stress and HO-1 induction by Ox-PAPC. Taken together, we demonstrated that the PMET system in HAEC plays an important role in the regulation of cellular redox status and HO-1 expression by Ox-PAPC.

【 授权许可】

Unknown