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NGF protects PC12 cells against ischemia by a mechanism that requires the N‐kinase
Author(s) -
Boniece I. R.,
Wagner John A.
Publication year - 1995
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490400102
Subject(s) - mechanism (biology) , ischemia , kinase , pharmacology , microbiology and biotechnology , chemistry , neuroscience , medicine , biology , philosophy , epistemology
Nerve growth factor (NGF), which has been shown to act as a morphological and neurochemical differentiating factor in PC12 cells, also protects PC12 cells from the toxicity of serum withdrawal and ischemia. By using a previously established in vitro model of ischemia, which incorporates the combination of anoxia with glucose deprivation (Boniece and Wagner: J Neurosci 13:4220–4228, 1993), we have been able to study the signal transduction pathways upon which NGF‐induced survival is dependent. Here we demonstrate that inhibitors of the N‐kinase and NGF‐induced neuritogenesis, 6‐thioguanine and 2‐aminopurine, prevent the protective effects of NGF, while they have little, if any, effect on the protection conferred by epidermal growth factor (EGF) or dbcAMP. This suggests that only NGF acts by a mechanism that depends strongly on the N‐kinase. Furthermore, the methyltransferase inhibitor 5′‐deoxy‐5′‐methylthioadenosine (MTA), which also inhibits NGF‐induced neuritogenesis, inhibits the protective effect of NGF but not the protective effects of EGF or dbcAMP. Thus, the neuroprotective effect of NGF requires some of the same signal transduction steps used by NGF to promote differentiation and neurite formation. Furthermore, we found that exposure of PC12 cells to retinoic acid, which promotes the differentiation and inhibits the growth of PC12 cells, also improves cell survival during ischemia. In addition, a combination of NGF and retinoic acid was more effective than either agent alone. It is likely that these two agents confer protection by independent pathways. © 1995 Wiley‐Liss, Inc.