Protective effect of selaginellin on glutamate-induced cytotoxicity and apoptosis in differentiated PC12 cells.
L-glutamate plays a key role in neuronal cell death associated with many neurodegenerative conditions such as cerebral ischemia, hypoxia, Alzheimer's, Huntington's, and Parkinson's diseases. Selaginellin, a component extracted from Saussurea pulvinata (Hook.et Grev.) Maximo, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by glutamate. The differentiated PC12 cells were pretreated with various concentrations (10(-7), 3 x 10(-7), or 10(-6) M) of selaginellin for 1 h prior to exposure to L-glutamate. Selaginellin was shown to protect PC12 cells against glutamate toxicity, as determined by characteristic morphological features, lactate dehydrogenase release and cell viability, and apoptosis as evaluated by Hoechst 33342 staining assay and caspase-3 activity. In addition, the increase in levels of reactive oxygen species and decrease in klotho gene expression induced by glutamate were significantly reversed by selaginellin. Our study suggests that selaginellin has a neuroprotective effect against L-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene.
Wang
Chen-Jing
CJ
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
Hu
Chang-Ping
CP
Xu
Kang-Ping
KP
Yuan
Qiong
Q
Li
Fu-Shuang
FS
Zou
Hui
H
Tan
Gui-Shan
GS
Li
Yuan-Jian
YJ
D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000633:toxicity*; D016716:PC12 Cells; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D030441:Saussurea
D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018698:Glutamic Acid