Open AccessBiphasic effect of aspirin on apoptosis of bovine vascular endothelial cells and its molecular mechanism
Author(s) -
CHEN Qingquan,
LIU Wenlan,
GUO Xun,
LI Yuanjian,
GUO Zhaogui
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00518.x
Subject(s) - mechanism (biology) , apoptosis , aspirin , microbiology and biotechnology , chemistry , pharmacology , cancer research , medicine , biology , biochemistry , philosophy , epistemology
Aim: 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 1 × 10 ‐10 mol/L to 1 × 10 ‐8 mol/L decreased the apoptosis and p38 MAPK phosphorylation induced by H 2 O 2 in BAEC, while high doses of aspirin (1 × 10 ‐7 ‐1 × 10 ‐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. Conclusion: Aspirin exhibits a biphasic effect on the apoptosis in BAEC, reducing apoptosis at low concentration and inducing apoptosis at high concentration. p38 MAPK maybe an important signal molecule mediating the effects of aspirin.