RRC ID 12178
Author Maeda Y, Ikeda U, Oya Ki, Shimpo M, Ueno S, Okada K, Saito T, Mano H, Ozawa K, Shimada K.
Title Endogenously generated nitric oxide by nitric-oxide synthase gene transfer inhibits cellular proliferation.
Journal J. Pharmacol. Exp. Ther.
Abstract We investigated whether endothelial nitrite oxide synthase (NOS) gene transfer inhibited cellular proliferation. Endothelial NOS and endothelin type A receptor genes were transferred into 293 cells, a human embryonic kidney cell line, by calcium-phosphate coprecipitation. The cytosolic free Ca(2+) levels ([Ca(2+)](i)) of transfected cells were estimated with fura-2 fluorescence. Thymidine incorporation was increased by endothelin-1 in type A receptor-transfected cells. The endothelial NOS gene transfer did not affect endothelin-1-induced increase in [Ca(2+)](i) of type A receptor-transfected cells, but markedly inhibited mitogen-activated protein kinase and c-fos promoter activities. The endothelial NOS gene transfer also inhibited thymidine incorporation into type A receptor-transfected cells in response to endothelin-1, which was abolished in the presence of the NOS inhibitor N(G)-monomethyl-L-arginine acetate. The endothelin-1-induced increase in cell number was significantly suppressed by endothelial NOS gene transfer as well as by the mitogen-activated protein kinase inhibitor PD98059. These results indicate that endothelial NOS gene transfer inhibits cellular proliferation via inhibition of the mitogen-activated protein kinase cascade.
Volume 292(1)
Pages 387-93
Published 2000-1
PMID 10604975
MeSH Calcium / metabolism Cell Division / physiology* Cells, Cultured Embryo, Mammalian Endothelin-1 / pharmacology Endothelium / physiology* Enzyme Inhibitors / pharmacology Flavonoids / pharmacology Fura-2 Humans In Vitro Techniques Kidney / physiology Mitogen-Activated Protein Kinases / metabolism NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / biosynthesis Nitric Oxide / physiology* Nitric Oxide Synthase / genetics* Phosphates / chemistry Proto-Oncogene Proteins c-fos / metabolism Receptors, Endothelin / genetics* Thymidine / pharmacokinetics Transfection
IF 3.615
Times Cited 14
DNA material Human ETB receptor cDNA Human endothelin-B receptor subtype cDNA (RDB01303) Human ETA receptor cDNA Human endothelin-A receptor subtype cDNA (RDB01302)