Atrial natriuretic peptide inhibits endothelin-1-induced activation of JNK in glomerular mesangial cells.
Atrial natriuretic peptide (ANP) has been shown to counteract various actions of endothelin-1 (ET-1) in mesangial cells. We have reported that both extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) are activated by ET-1 and ET-1-induced activation of ERK is inhibited by ANP. To further clarify the action of ANP, we examined the effect of ANP on ET-1-induced activation of JNK. ANP inhibited ET-1-induced activation of JNK in a dose-dependent manner. This inhibitory effect of ANP was reversed by HS-142-1, an antagonist for biological receptors of ANP, while C-ANP, an analog specific to clearance receptors of ANP, failed to inhibit ET-1-induced activation of JNK. 8-Bromo-cGMP and sodium nitroprusside were also able to inhibit ET-1-induced activation of JNK, suggesting cGMP-dependent action of ANP. In contrast, ANP failed to inhibit interleukin-1 beta (IL-1 beta)-induced activation of JNK. Since an increase in intracellular calcium ([Ca2+]i) was shown to be necessary for ET-1-induced activation of JNK in mesangial cells, we measured [Ca2+]i using fura-2. ANP attenuated the ET-1-induced increase in [Ca2+]i in concentrations enough to inhibit ET-1-induced activation of JNK. Finally, ANP was able to inhibit ET-1-, but not IL-1 beta-induced increase in DNA-binding activity of AP-1 by gel shift assay. These results indicate that ANP is able to inhibit ET-1-induced activation of AP-1 by inhibiting both ERK and JNK, suggesting that ANP might be able to counteract the expression of AP-1-dependent genes induced by ET-1.
Isono
M
M
Third Department of Medicine, Shiga University of Medical Science, Japan.
Haneda
M
M
Maeda
S
S
Omatsu-Kanbe
M
M
Kikkawa
R
R
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D019332:Endothelin-1; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; D018808:Transcription Factor AP-1; D009320:Atrial Natriuretic Factor; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D006152:Cyclic GMP; D002118:Calcium