Journal
BIOCHEMICAL PHARMACOLOGY
Volume 59, Issue 11, Pages 1477-1487Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(00)00275-6
Keywords
LDL; oxidation; alpha-tocopherol; gamma-tocopherol; apoptosis; SMC; CHD
Categories
Ask authors/readers for more resources
Apoptosis may play an important role in atherogenesis. Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in the arterial a all in addition to several other proatherogenic effects. Tocopherol supplements have been suggested to protect against coronary heart disease (CHD) in epidemiological studies. The effects of oxLDL and alpha- and gamma-tocopherol on apoptotic signaling pathways are poorly understood. Thus, the goal of the study was to investigate these pathways in the presence of copper-oxidized LDL and tocopherols in human coronary smooth muscle cells (SMC). We showed that oxLDL-mediated apoptosis, assessed by DNA fragmentation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, and caspase activation stimulated several transcription factors and proapoptotic dynamic movements of the Bcl-2 family proteins through the mitogen-activated protein kinase (MAPK) and Jun kinase pathways. alpha-Tocopherol and gamma-tocopherol significantly reduced these molecular events and cell death effectors caspase-3 and -8. Under our experimental conditions, alpha-tocopherol was significantly more effective than gamma-tocopherol, and oxLDL-mediated apoptosis increased c-Jun, cyclic AMP-responsive element-binding, Ets-like element kinase dependent 7, and activating transcription factor-2 proteins as well as nuclear activity of the activated protein-1 complex in human coronary SMC. Moreover, our results demonstrate that tocopherols may exert their antiatherogenic effects at least in part via reduction of the MAPK and JunK cascade together with a protective profile of apoptotic genes of the Bcl-2 family. These data are consistent with the beneficial effects of tocopherols on atherogenesis seen in experimental studies and on CHD in epidemiological surveys. BIOCHEM PHARMACOL 59;11:1477-1487, 2000. (C) 2000 Elsevier Science Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available