Open AccessInhibition of caspases and intracellular free Ca 2+ concentrations are involved in resveratrol protection against apoptosis in rat primary neuron cultures 1
Author(s) -
GONG Qihai,
WANG Qian,
SHI Jingshan,
HUANG Xienan,
LIU Qiong,
MA Hu
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.1745-7254.2007.00666.x
Subject(s) - apoptosis , intracellular , caspase , neuron , resveratrol , microbiology and biotechnology , programmed cell death , biology , caspase 3 , chemistry , pharmacology , neuroscience , biochemistry
Aim: To investigate the influence of resveratrol (Res), a nutritional antioxidant, on the inhibition of apoptosis in rat primary neuron cultures. Methods: The cultured cortical neurons of neonatal Sprague‐Dawley rats were pretreated with Res (0.1, 1.0, and 10.0 μmol/L) and oxygen‐glucose deprivation/reperfusion (OGD/RP) with oxygen and glucose were initiated at d 10 in vitro. Neuronal apoptosis was determined by flow cytometry, and morphological changes of neurons were observed by an electron microscope. For the mechanism studies, the intracellular free calcium concentration ([Ca 2+ ] i ) and the transcription of caspases‐3 and ‐12 in neurons were detected by Fura 2/AM loading and real‐time RT‐PCR, respectively. Results: OGD/RP insult could induce an increase in the apoptotic rate of neurons (from 11.1% to 49.0%), and elicit an obvious morphological change in neurons; pretreatments with Res (0.1, 1.0, and 10.0 μmol/L, respectively) significantly reduced the elevated rate of apoptosis to 41.7%, 40.8%, and 37.4%, respectively, and ameliorated the neuronal morphological injury. Similarly, the OGD/RP insult obviously elicited the elevated levels of the [Ca 2+ ] i and the expressions of caspases‐3 and ‐12 mRNA in neurons. Res pretreatments markedly depressed the neuronal abnormal elevation of [Ca 2+ ] i and the overexpression of caspases‐3 and ‐12 mRNA in a concentration‐dependent manner. Conclusion: Res can attenuate the rat cortical neuronal apoptosis induced by OGD/RP. The mechanisms are, at least partly, due to the inhibition of the calcium overload and the overexpression of caspases‐3 and ‐12 mRNA.