Apoptosis of cerebellar granule cells induced by serum withdrawal, glutamate or β-amyloid, is independent of Jun kinase or p38 mitogen activated protein kinase activation

1998 ◽  
Vol 250 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Frank J. Gunn-Moore ◽  
Jeremy M. Tavaré
1997 ◽  
Vol 324 (2) ◽  
pp. 365-369 ◽  
Author(s):  
Frank J. GUNN-MOORE ◽  
Alan G. WILLIAMS ◽  
Nicholas J. TOMS ◽  
Jeremy M. TAVARÉ

We have investigated the role of mitogen-activated protein (MAP) kinase in the survival of cerebellar granule cells in primary culture. Brain-derived neurotrophic factor (BDNF) and insulin, but not epidermal growth factor (EGF), promoted the survival of P6 cerebellar granule neurons. BDNF promoted a sustained activation of MAP kinase, whereas that induced by EGF was only transient. Insulin promoted a small but transient activation of MAP kinase that was completely blocked by PD98059, an inhibitor of MAP kinase kinase activation. PD98059 had no effect on the insulin- or BDNF-induced survival of cerebellar granule cells. We also investigated the role of p70S6 kinase in survival. The activation of p70S6 kinase by EGF was transient, whereas BDNF and insulin promoted a sustained activation of p70S6 kinase. Rapamycin, which blocked p70S6 kinase activation, had no effect on the BDNF- or insulin-induced survival of cerebellar granule cells. We conclude that sustained activation of MAP kinase is not correlated with the survival response of cerebellar granule cells; indeed insulin-mediated survival is independent of MAP kinase. Survival of cerebellar granule cells is also independent of the activation of p70S6 kinase.


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