Submitted on July 14, 2008
Revised on August 6, 2008
Accepted on September 4, 2008
Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells
Gyeong In Mun1, Sang Mi An1, Heonyong Park2, Hanjoong Jo3, and Yong Chool Boo1*
1 Kyungpook National University
2 Dankook University
3 Emory University
* To whom correspondence should be addressed. E-mail: ycboo{at}knu.ac.kr.
Elevated blood glucose and free fatty acids induce oxidative stress associated with the incidence of cardiovascular disease. In contrast, laminar shear stress (LSS) plays a critical role in maintaining vascular health. The present study examined mechanism for the antioxidant effect of LSS attenuating the oxidative stress induced by high glucose (HG) and arachidonic acid (AA) in human umbilical vein endothelial cells. HG and AA synergistically decreased cell viability and increased glutathione (GSH) oxidation and lipid peroxidation. The lipid peroxidation was markedly prevented by LSS as well as tetrahydrobiopterin (BH4) and GSH. LSS increased BH4 and GSH contents, and expression of GTP cyclohydrolase-1 and glutamylcysteine ligase (GCL) involved in their biosynthesis. Inhibition of GCL activity by DL-buthionine-(S,R)-sulfoximine and siRNA-mediated knockdown of GCL lessened the antioxidant effect of LSS. Therefore it is suggested that LSS enhances antioxidant capacity of endothelial cells, and thereby attenuates the oxidative stress caused by cardiovascular risk factors.
