Inhibitors of p38 mitogen-activated protein kinase promote neuronal survival in vitro
- PMID: 9589393
- DOI: 10.1002/(SICI)1097-4547(19980515)52:4<483::AID-JNR12>3.0.CO;2-4
Inhibitors of p38 mitogen-activated protein kinase promote neuronal survival in vitro
Abstract
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 IC50 (approximately 30 microM) 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.
Similar articles
-
An inhibitor of p38 and JNK MAP kinases prevents activation of caspase and apoptosis of cultured cerebellar granule neurons.Jpn J Pharmacol. 1999 Mar;79(3):369-78. doi: 10.1254/jjp.79.369. Jpn J Pharmacol. 1999. PMID: 10230866
-
CEP-1347/KT7515, a JNK pathway inhibitor, supports the in vitro survival of chick embryonic neurons.Neuroreport. 1998 May 11;9(7):1435-9. doi: 10.1097/00001756-199805110-00034. Neuroreport. 1998. PMID: 9631443
-
Role of mitogen-activated protein kinases in S-nitrosoglutathione-induced macrophage apoptosis.Biochemistry. 1999 Feb 23;38(8):2279-86. doi: 10.1021/bi982292a. Biochemistry. 1999. PMID: 10029520
-
MAPKs as mediators of cell fate determination: an approach to neurodegenerative diseases.Curr Med Chem. 2008;15(6):538-48. doi: 10.2174/092986708783769731. Curr Med Chem. 2008. PMID: 18336268 Review.
-
Oxygen toxicity induces apoptosis in neuronal cells.Cell Mol Neurobiol. 1998 Dec;18(6):649-66. doi: 10.1023/a:1020633919115. Cell Mol Neurobiol. 1998. PMID: 9876872 Free PMC article. Review.
Cited by
-
The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta -arrestin-dependent scaffolding complex.Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11086-91. doi: 10.1073/pnas.190276697. Proc Natl Acad Sci U S A. 2000. PMID: 10995467 Free PMC article.
-
Stress-responsive JNK mitogen-activated protein kinase mediates aspirin-induced suppression of B16 melanoma cellular proliferation.Br J Pharmacol. 2003 Mar;138(6):1156-62. doi: 10.1038/sj.bjp.0705163. Br J Pharmacol. 2003. PMID: 12684272 Free PMC article.
-
14-3-3 proteins block apoptosis and differentially regulate MAPK cascades.EMBO J. 2000 Feb 1;19(3):349-58. doi: 10.1093/emboj/19.3.349. EMBO J. 2000. PMID: 10654934 Free PMC article.
-
How protein kinase C activation protects nerve cells from oxidative stress-induced cell death.J Neurosci. 2001 May 1;21(9):2929-38. doi: 10.1523/JNEUROSCI.21-09-02929.2001. J Neurosci. 2001. PMID: 11312276 Free PMC article.
-
Influence of temperature on the ontogenetic expression of neural development-related genes from developing tilapia brain expressed sequence tags.Mar Biotechnol (NY). 2007 Mar-Apr;9(2):243-61. doi: 10.1007/s10126-006-6089-2. Epub 2007 Jan 24. Mar Biotechnol (NY). 2007. PMID: 17252285
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous