Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells.
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 the 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 small-interfering RNA-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.
Mun
Gyeong In
GI
Department of Molecular Medicine, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.
An
Sang Mi
SM
Park
Heonyong
H
Jo
Hanjoong
H
Boo
Yong Chool
YC
D016718:Arachidonic Acid / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006136:GTP Cyclohydrolase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013314:Stress, Mechanical
D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D001708:Biopterins; D016718:Arachidonic Acid; D019328:Buthionine Sulfoximine; D006136:GTP Cyclohydrolase; D005721:Glutamate-Cysteine Ligase; C003402:sapropterin; D005978:Glutathione; D005947:Glucose
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