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Tumor Necrosis Factor α Activates the Phosphorylation of ERK, SAPK/JNK, and P38 Kinase in Primary Cultures of Neurons

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Abstract

Emerging data indicate that the inflammatory cytokine TNFα exerts a neuroprotective effect against brain injury. To better understand the mechanism of action of TNFα on neurons we have investigated the possible activation of various MAP kinases. Exposure of neurons to TNFα 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 TNFα-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 TNFαsignaling in neurons involved the acidic sphingomyelinase.

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Barbin, G., Roisin, M.P. & Zalc, B. Tumor Necrosis Factor α Activates the Phosphorylation of ERK, SAPK/JNK, and P38 Kinase in Primary Cultures of Neurons. Neurochem Res 26, 107–112 (2001). https://doi.org/10.1023/A:1011086426652

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