| 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 |
2000-1-1
|
| 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 |
3.561
|
| Times Cited |
15
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
| Resource |
| DNA material |
Human ETB receptor cDNA Human endothelin-B receptor subtype cDNA (RDB01303)
Human ETA receptor cDNA Human endothelin-A receptor subtype cDNA (RDB01302) |
