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   Endogenous nitric oxide generation linked to ryanodine receptors activates cyclic GMP / protein kinase G pathway for cell proliferation of neural stem/progenitor cells derived from embryonic hippocampus  
   
نویسنده yoneyama m. ,kawada k. ,shiba t. ,ogita k.
منبع journal of pharmacological sciences - 2011 - دوره : 115 - شماره : 2 - صفحه:182 -195
چکیده    Nitric oxide (no) activates the cyclic gmp (cgmp) / protein kinase g (pkg) pathway during physiological processes in numerous types of cells. here,we evaluated whether this no/cgmp/pkg pathway is involved in the proliferation of neural stem/progenitor cells (npcs) derived from the hippocampus of embryonic mice. in culture,the exposure to the no synthase inhibitor n ω-nitro-l-arginine methyl ester (l-name) significantly decreased the number of viable cells and 5-bromo-2′-deoxyuridine (brdu) incorporation into the cells,as well as the levels of intracellular reactive oxygen species,extracellular no 2,and intracellular cgmp. like l-name,the soluble guanylate cyclase inhibitor 1h-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (odq) and pkg inhibitor kt5823 also decreased cell viability and brdu incorporation. the membrane-permeable cgmp analogue 8-bromo-cgmp partially abolished the l-name-induced decrease in the brdu incorporation. brdu incorporation was decreased by ca 2+-channel blockers,including dantrolene,mk-801,ifenprodil,and nifedipine. interestingly,the no 2 level was decreased by dantrolene,but not by the other 3 blockers. l-name and odq attenuated phosphorylation of akt,but not that of extracellular signal-regulated kinases or epidermal growth factor receptors. our data suggest that endogenous no generation linked to dantrolene-sensitive ryanodine receptors activates the cgmp/pkg signaling pathway for positive regulation of proliferation of hippocampal npcs derived from embryonic mice. © the japanese pharmacological society.
کلیدواژه Cyclic GMP / protein kinase G pathway; Neural stem/progenitor cells; Nitric oxide; Proliferation; Ryanodine receptor channel
آدرس department of pharmacology,setsunan university faculty of pharmaceutical sciences,hirakata,osaka 573-0101, Japan, department of pharmacology,setsunan university faculty of pharmaceutical sciences,hirakata,osaka 573-0101,japan,department of pharmacology,faculty of pharmacy,chiba institute of science,shiomi-cho,choshi,chiba 288-0025, Japan, department of pharmacology,setsunan university faculty of pharmaceutical sciences,hirakata,osaka 573-0101, Japan, department of pharmacology,setsunan university faculty of pharmaceutical sciences,hirakata,osaka 573-0101, Japan
 
     
   
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