Rutaecarpine inhibits hypoxia/reoxygenation-induced apoptosis in rat hippocampal neurons.
Our previous studies showed that rutaecarpine (Rut) protected against myocardial ischemia/reperfusion (I/R) injury, which was associated with activation of transient receptor potential vanilloid subtype 1 (TRPV1). Recently, TRPV1 activation was also reported to exert neuroprotective effects. The present study was to investigate the effect of Rut on hypoxia/reoxygenation (H/R)-induced apoptosis in primary rat hippocampal neurons. Three-hour hypoxia (1% O2) and consequent 24-h reoxygenation significantly increased the apoptotic death of hippocampal neurons as evidenced by increases in both TUNEL-positive cell number and caspase-3 activity. However, pretreatment with Rut (1-10microM) or caspase-3 specific inhibitor DEVD-CHO could markedly attenuate H/R-induced apoptosis in neurons. Rut markedly induced the phosphorylation of Akt and PI3K inhibitor LY294002 prevented the survival effect of Rut on neurons. Intracellular oxidative stress was significantly induced after H/R, which was inhibited by Rut and LY294002 as well as antioxidant PDTC. TRPV1 antagonist capsazepine or intracellular Ca2+ chelator BAPTA/AM could abolish these effects of Rut mentioned above. In summary, the present data suggest that Rut inhibits H/R-induced apoptosis of hippocampal neurons via TRPV1-[Ca2+]i-dependent and PI3K/Akt signaling pathway, which is related to inhibiting oxidative stress and caspase-3 activation.
Dai
Zhong
Z
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 110 Xiang-Ya Road, Changsha 410078, China.
Xiao
Jian
J
Liu
Si-Yu
SY
Cui
Liao
L
Hu
Gao-Yun
GY
Jiang
De-Jian
DJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D000860:Hypoxia / Q000378:metabolism*; D020287:In Situ Nick-End Labeling / Q000379:methods; D026121:Indole Alkaloids / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D052999:Quinazolinones
D053148:Caspase 3; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D010100:Oxygen; D011799:Quinazolines; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; C028632:rutecarpine; D052999:Quinazolinones