Guo Shi-Yin, Yang Guo-Ping, Jiang De-Jian, Wang Feng, Song Tao, Tan Xing-He, Sun Zhen-Qiu
School of Public Health, Central South University, Xiang-Ya Road 110, Changsha 410078, China.
Can J Physiol Pharmacol. 2008 Nov;86(11):785-92. doi: 10.1139/Y08-083.
The aim of this study was to investigate the effect of capsaicin on hypoxia-reoxygenation (H/R)-induced apoptosis in primary rat hippocampal neurons. Three hours of hypoxia (1% O2) and subsequent reoxygenation for 24 h significantly increased the apoptotic death of hippocampal neurons, as evidenced by increases in both TUNEL-positive cell number and caspase-3 activity. Pretreatment with capsaicin (3-30 micromol/L) or the caspase-3-specific inhibitor acetyl-DEVD-CHO (100 micromol/L) markedly attenuated H/R-induced apoptosis in hippocampal neurons. Capsaicin also markedly induced the phosphorylation of Akt. The phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (10 micromol/L) prevented any capsaicin-induced survival effect in hippocampal neurons. Intracellular levels of reactive oxygen species (ROS), which were greatly increased after H/R, were significantly inhibited by capsaicin, pyrrolidine dithiocarbamate (PDTC) (50 micromol/L), and LY294002. Taken together, these data suggest that capsaicin protects against H/R-induced apoptosis of hippocampal neurons via the PI3K/Akt-mediated signaling pathway, which is related to the inhibition of oxidative stress and caspase-3 activation.
