Biphasic effect of aspirin on apoptosis of bovine vascular endothelial cells and its molecular mechanism.
OBJECTIVE
To investigate the effect of aspirin on the apoptosis of cultured bovine aortic endothelial cells (BAEC) and the signal pathways involved in this process.


METHODS
BAEC were cultured and passaged in Dulbecco's modified Eagle's medium culture medium. Morphologic changes and quantification of apoptotic cells were determined using fluorescence microscope after staining the cells with Hoechst 33258. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) method. DNA fragmentation was visualized by agarose gel electrophoresis. Phospho-p38 mitogen-activated protein kinase (MAPK) expression was detected by Western blotting.


RESULTS
Aspirin at low concentrations from 1X10( -10) mol/L to 1X10( -8) mol/L decreased the apoptosis and p38 MAPK phosphorylation induced by H2O2 in BAEC, while high doses of aspirin (1X10( -7)-1X10( -4) mol/L) induced typical apoptotic changes in BAEC and stimulated the expression of phospho-p38 MAPK in a concentration-dependent manner. SB203580, a specific p38 MAPK inhibitor, blocked such effects.


CONCLUSIONS
Aspirin exhibits a biphasic effect on the apoptosis in BAEC, reducing apoptosis at low concentration and inducing apoptosis at high concentration. p38 MAPK may be an important signal molecule mediating the effects of aspirin.
Chen
Qing-Quan
QQ
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Liu
Wen-Lan
WL
Guo
Xun
X
Li
Yuan-Jian
YJ
Guo
Zhao-Gui
ZG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001241:Aspirin / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
D016861:Cyclooxygenase Inhibitors; D004247:DNA; D048051:p38 Mitogen-Activated Protein Kinases; D001241:Aspirin