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Inhibitors of p38 mitogen‐activated protein kinase promote neuronal survival in vitro
Author(s) -
Horstmann Sonja,
Kahle Philipp J.,
Borasio Gian Domenico
Publication year - 1998
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/(sici)1097-4547(19980515)52:4<483::aid-jnr12>3.0.co;2-4
Subject(s) - p38 mitogen activated protein kinases , kinase , microbiology and biotechnology , protein kinase a , mitogen activated protein kinase , biology , ribosomal s6 kinase , nerve growth factor , ask1 , in vitro , mitogen activated protein kinase kinase , signal transduction , biochemistry , protein kinase b , p70 s6 kinase 1 , receptor
Mammalian mitogen‐activated protein kinases include the extracellular signal‐regulated protein kinase, the c‐ Jun amino‐terminal kinase, and the p38 subgroups. Sustained activation of Jun kinase and p38 have been shown to precede apoptosis of PC12 pheochromocytoma cells induced by withdrawal of trophic factors. To investigate the possible role of p38 in neuronal apoptosis, we tested the effect of two selective p38 inhibitors, the pyridinyl imidazole compounds SB203580 and SB202190, on different populations of chick embryonic neurons in vitro. Both substances promoted the in vitro survival of sensory, sympathetic, ciliary and motor neurons in a dose‐dependent fashion. When assayed in nerve growth factor‐stimulated PC12 cells, SB203580 pretreatment inhibited the activation of both ribosomal S6 kinases‐1 and ‐2 with the same IC 50 (approximately 30 μM) that inhibited apoptosis in primary neurons. Thus, p38 inhibitor‐sensitive pathways may be involved in apoptosis of neurotrophic factor‐deprived primary neurons, and in activation of ribosomal S6 kinases. J. Neurosci. Res. 52:483–490, 1998. © 1998 Wiley‐Liss, Inc.