Protection of capsaicin against hypoxia-reoxygenation-induced apoptosis of rat hippocampal neurons.
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.
Guo
Shi-Yin
SY
School of Public Health, Central South University, Xiang-Ya Road 110, Changsha 410078, China.
Yang
Guo-Ping
GP
Jiang
De-Jian
DJ
Wang
Feng
F
Song
Tao
T
Tan
Xing-He
XH
Sun
Zhen-Qiu
ZQ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology
D002211:Capsaicin; D053148:Caspase 3; D061945:Caspase Inhibitors; D002867:Chromones; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011392:Proline; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one