Protective effects of YC-1 against glutamate induced PC12 cell apoptosis.
Glutamate, one of the major neurotransmitters in the central nervous system, is released into the synaptic spaces and bound to the glutamate receptors which facilitate normal synaptic transmission, synaptic plasticity, and brain development. Past studies have shown that glutamate with high concentration is a potent neurotoxin capable of destroying neurons through many signal pathways. In this research, our main purpose was to determine whether the specific soluble guanylyl cyclase activator YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole) had effect on glutamate-induced apoptosis in cultured PC12 cells. The differentiated PC12 cells impaired by glutamate were used as the cell model of excitability, and were exposed to YC-1 or/and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) with gradient concentrations for 24 h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl) assay was used to detect the cellular viability. Radioimmunoassay (RIA) was used to detect the cGMP (cyclic guanosine monophosphate) concentrations in PC12 cells. Hoechst 33258 staining and flow cytometric analysis were used to detect the cell apoptosis. The cellular viability was decreased and the apoptotic rate was increased when PC12 cells were treated with glutamate. Cells treated with YC-1 or/and ODQ showed no significant differences in the cell viability and intracellular cGMP levels compared with those of control group. The specific soluble guanylyl cyclase (sGC) inhibitor ODQ showed an inhibitory effect on cGMP level and aggravated the apoptosis of PC12 cells induced by glutamate. YC-1 elevated cGMP level thus decreased PC12 cell apoptosis induced by glutamate, but this effect could be reversed by ODQ. These results revealed that YC-1 might attenuate glutamate-induced PC12 cell apoptosis via a sGC-cGMP involved pathway.
College of Medicine, Nankai University, Tianjin, China.
Xiaofan
X
Yang
Yucheng
Y
Wang
Jia
J
Luo
Shichang
S
Liu
Zhuo
Z
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006152:Cyclic GMP / Q000096:biosynthesis; D004357:Drug Synergism; D005971:Glutamates / Q000633:toxicity*; D007191:Indazoles / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D016716:PC12 Cells; D020011:Protective Agents / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D013194:Staining and Labeling
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D005971:Glutamates; D007191:Indazoles; D010069:Oxadiazoles; D020011:Protective Agents; D011810:Quinoxalines; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D006152:Cyclic GMP; D006690:Bisbenzimidazole