Nitric oxide modulates the c-Jun N-terminal kinase/stress-activated protein kinase activity through activating c-Jun N-terminal kinase kinase.
Nitric oxide is a signaling molecule that has a broad range of physiological functions, including neurotransmission, macrophage activation, and vasodilation. The mechanism by which nitric oxide regulates signal transduction mediating diverse biological activities is not fully understood, however. Here, we demonstrate that nitric oxide induced the stimulation of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) in intact cells. Exposure of cultured HEK293 cells to sodium nitroprusside, a nitric oxide releasing agent, resulted in the stimulation of JNK1 activity. The sodium nitroprusside-induced stimulation of JNK1 activity was abolished by treatment of cells with N-acetylcysteine. Nitric oxide production from HEK293 cells ectopically expressing nitric oxide synthases resulted in the stimulation of JNK1 activity, while JNK1 stimulation in nitric oxide synthase-overexpressing cells was abrogated by a nitric oxide synthase inhibitor, NG-nitro-L-arginine. Furthermore, exposure of cells to sodium nitroprusside resulted in the stimulation of JNK kinase (JNKK1/SEK1). Taken together, our data suggest that nitric oxide modulates the JNK activity through activating JNKK1/SEK1.
Kim
H
H
Cell Biology and Molecular Genetics Laboratories, Hanhyo Institute of Technology, Taejon, Korea.
Shim
J
J
Han
P L
PL
Choi
E J
EJ
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney; D048670:MAP Kinase Kinase 4; D017628:Microglia; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D013312:Stress, Physiological / Q000201:enzymology; D014162:Transfection
D005609:Free Radicals; D009599:Nitroprusside; D009569:Nitric Oxide; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases