Tumor necrosis factor alpha activates the phosphorylation of ERK, SAPK/JNK, and P38 kinase in primary cultures of neurons.
Emerging data indicate that the inflammatory cytokine TNFalpha exerts a neuroprotective effect against brain injury. To better understand the mechanism of action of TNFalpha on neurons we have investigated the possible activation of various MAP kinases. Exposure of neurons to TNFalpha triggered the rapid phosphorylation of three members of the MAP kinase family, i.e., extracellular signal-regulated kinase (ERK1/2), stress-activated protein kinase/JUN N-terminal kinase (SAPK/JNK) and the p38 kinase; this activation occured with the same time course and was transient. The TNFalpha-induced activation of ERK1/2 was specifically prevented by compound PD 98059 a specific inhibitor of the MAP kinase kinase MEK1/2. Activation of ERK1/2 was also specifically inhibited by the xanthogenic derivative D609, a specific inhibitor of phosphoinositide phospholipase C suggesting that TNFalpha signaling in neurons involved the acidic sphingomyelinase.
Barbin
G
G
INSERM U. 495, Paris, France. barbin@ccr.jussieu.fr
Roisin
M P
MP
Zalc
B
B
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases