gamma-tocopherol decreases ox-LDL-mediated activation of nuclear factor-kappaB and apoptosis in human coronary artery endothelial cells.
gamma-Tocopherol, produced by many plants, is the major form of tocopherol in the United States diet. It is an effecient protector of lipids against peroxidative damage. Epidemiologic studies show that supplementation of diet with gamma-tocopherol is inversely related to the risk of death from cardiovascular disease. This study was conducted to examine the role of gamma-tocopherol in oxidized LDL (ox-LDL)-induced nuclear factor (NF)-kappaB activation and apoptosis in human coronary artery endothelial cells (HCAECs). Cultured HCAECs were treated with ox-LDL (10-40 microgram/ml). Incubation of HCAECs with ox-LDL resulted in apoptosis of HCAECs, as determined by TUNEL and DNA laddering. Ox-LDL degraded IkappaB protein and activated NF-kappaB in HCAECs (both P < 0.01 vs control), as determined by Western blot. Treatment of cells with gamma-tocopherol attenuated ox-LDL-mediated degradation of IkappaB and activation of NF-kappaB (both P < 0.01 vs ox-LDL alone). The presence of gamma-tocopherol also reduced ox-LDL-induced apoptosis (P < 0.01 vs ox-LDL alone). A high concentration of gamma-tocopherol (50 micromol/L) was more effective than the low concentration of gamma-tocopherol (10 micromol/L) in this process. These observations show that ox-LDL induces apoptosis of HCAECs at least partially by activation of NF-kappaB signal transduction pathway. gamma-Tocopherol significantly decreases ox-LDL-induced apoptosis of HCAECs by inhibiting the activation of NF-kappaB.
Li
D
D
Department of Medicine and Department of Physiology, University of Florida and VA Medical Center, Gainesville, Florida, USA.
Saldeen
T
T
Mehta
J L
JL
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins; D008077:Lipoproteins, LDL / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C099252:oxidized low density lipoprotein; D000072000:NF-KappaB Inhibitor alpha; D014810:Vitamin E