title: Lipolytic inhibitor G0/G1 switch gene 2 inhibits reactive oxygen species production and apoptosis in endothelial cells.
abstract: G0/G1 switch gene 2 (G0S2), a novel target gene of peroxisome proliferator-activated receptor, is highly expressed in fat tissues. G0S2 acts as proapoptotic factor toward human cancer cells. Endothelial cell (EC) apoptosis may be an initiating event in the development of atherosclerosis. However, the expression and function of G0S2 in vascular ECs remain unknown. Here, we reported for the first time that G0S2 is expressed in arterial ECs. Ectopic expression of G0S2 increased neutral lipid accumulation in cultured ECs. However, G0S2 prevented ECs from serum-free starvation stress- and hydrogen peroxide (H2O2)-induced apoptosis. G0S2 blocked the H2O2-induced dissipation of mitochondrial membrane potential. G0S2 decreased the release of cytochrome c from mitochondria into the cytosol, followed by activation of caspase-9 and caspase-3. The anti-apoptotic effect of G0S2 was Bcl-2 and adipose triglyceride lipase independent. In contrast, gene silence of G0S2 increased serum-free starvation stress-induced EC apoptosis and decreased the formation of capillary-like structures. We further found that G0S2 couples with the F0F1-ATP synthase in ECs. Levels of ATP were elevated, whereas reactive oxygen species levels were reduced in G0S2-expressing ECs. G0S2 can inhibit endothelial denudation secondary to H2O2-induced injury to ECs in vivo. These results indicate that G0S2 acts as a prosurvival molecule in ECs. Taken together, our results indicate that G0S2 has a protective function in ECs and may be a potential target for the treatment of cardiovascular diseases associated with reactive oxygen species-induced EC injury, such as atherosclerosis and restenosis.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China;
authors.forename: Yinfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Hubei University of Medicine, Hubei, China; and.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China;
authors.forename: Yichun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China zhangnep@hotmail.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; C508073:G0S2 protein, human; C586945:G0S2 protein, rat; D016877:Oxidants; D017382:Reactive Oxygen Species; D006180:Proton-Translocating ATPases
keywords: G0S2; apoptosis; atherosclerosis; endothelial cell; mitochondria