Mechanisms of selenium inhibition of cell apoptosis induced by oxysterols in rat vascular smooth muscle cells.
Our previous study reported that oxysterol cholestane-3beta,5 alpha, 6 beta-triol (Triol) induced vascular smooth muscle cells (VSMCs) apoptosis, which was inhibited by selenium pretreatment. To further investigate the mechanisms of the inhibition, the glutathione peroxidase (GPx) activity, the total antioxidant capacity (T-AOC), the total superoxide dismutase (SOD) activity, and the level of lipid peroxidation (the content of malondialdehyde, MDA) of VSMCs were measured, and fluidity of cell membrane, reactive oxygen species (ROS) level, the reduction of mitochondrial membrane potential (Delta psi(m)), and the intracellular Ca(2+) in single cell were detected using several fluorescence indicators. Meanwhile, the mRNA levels of c-myc, bcl-2, GPx, and thioredoxin reductase (TR) were measured by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results showed that the decrease of GPx activity, T-AOC, SOD activity, the fluidity of cell membrane, the Delta psi(m), and the mRNA expression of c-myc, bcl-2, GPx, and TR of VSMCs and the increase of MDA, ROS generation, and intracellular Ca(2+), significantly induced by Triol (10 microM, 24h) were inhibited to a different extent, respectively, when cells were pretreated with sodium selenite (50 nM, 12 or 24h) before exposure to Triol. These effects were time dependent and enhanced with prolongation of the time of pretreatment. In conclusion, the results in the present work showed that the mechanism of selenium inhibition of cell apoptosis induced by oxysterols in rat VSMCs was related with the antioxidation of selenoproteins.
Tang
Rong
R
Department of Chemistry, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
Liu
Hongmei
H
Wang
Tiebing
T
Huang
Kaixun
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002777:Cholestanols / Q000494:pharmacology*; D004338:Drug Combinations; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology*; D013261:Sterols / Q000494:pharmacology
D002777:Cholestanols; D004338:Drug Combinations; D017382:Reactive Oxygen Species; D013261:Sterols; C000474:cholestane-3,5,6-triol; D012643:Selenium