Endothelin-1 stimulates c-fos mRNA expression in C6 glioma cells via MAP kinase pathway.
Exposure of C6 glioma cells to endothelin-1 (ET-1) caused dose-dependent (10(-11) M to 10(-7) M) increments in intracellular calcium concentration ([Ca2+]i) and c-fos mRNA expression (4.5-fold) that were abolished by the endothelinA receptor antagonist, BQ610, and by inhibition of phospholipase C with U73122. ET-1 stimulated c-fos mRNA expression was also inhibited by protein kinase C inhibition (chelerythrine) and by the MAP kinase kinase inhibitor PD98059, but not by inhibitors of tyrosine kinases, protein kinase A type I or II, calmodulin kinase II, or calcium channel blockade. C6 cells treated with ET-1 demonstrated a significant increase in MAP kinase activity as evidenced by Western blotting. These results indicate a mechanism of long-term signaling by ET-1 involving an ET(A) receptor-mediated, phospholipase C(beta)-linked pathway that is dependent on protein kinase C and MAP kinase activation.
Leach
K
K
Department of Surgery and The Michigan Peptide Research Center, University of Michigan Medical School, Ann Arbor, USA.
Turner
D
D
Zhang
W
W
Mulholland
M W
MW
D000470:Alkaloids; D053119:Benzophenanthridines; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010766:Phosphorylation; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D053119:Benzophenanthridines; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D004963:Estrenes; D005419:Flavonoids; D009842:Oligopeptides; D010617:Phenanthridines; D011760:Pyrrolidinones; D012333:RNA, Messenger; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C087220:BQ 610; C016299:chelerythrine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one