Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway.
Neurotrophic factor deprivation causes apoptosis by a mechanism that requires macromolecular synthesis. This fact suggests that gene expression is necessary to achieve cell death. To identify mRNA that is expressed in apoptotic cells we used subtractive hybridization with cDNA prepared from neuronal pheochromocytoma cells. Monoamine oxidase (MAO) expression was increased in cells during nerve growth factor withdrawal-induced apoptosis. The increased apoptosis and induction of MAO was prevented by inhibition of the p38 mitogen-activated protein (MAP) kinase pathway. MAO may contribute to the apoptotic process because inhibition of MAO activity suppressed cell death. Together, these data indicate that MAO may be a target of pro-apoptotic signal transduction by the p38 MAP kinase pathway.
De Zutter
G S
GS
Program in Molecular Medicine and Howard Hughes Medical Institute, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
Davis
R J
RJ
D000818:Animals; D017209:Apoptosis; D004298:Dopamine / Q000494:pharmacology; D015870:Gene Expression; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics; D016716:PC12 Cells; D051381:Rats; D050825:Synaptosomal-Associated Protein 25; D048051:p38 Mitogen-Activated Protein Kinases
D008565:Membrane Proteins; D008996:Monoamine Oxidase Inhibitors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D008995:Monoamine Oxidase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004298:Dopamine