Related Experiment Videos
Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway
1Program in Molecular Medicine and Howard Hughes Medical Institute, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
Abstract:
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.
Insights
Neurotrophic factor deprivation triggers apoptosis, requiring gene expression. Monoamine oxidase (MAO) is upregulated during this process and may be a target of the p38 MAP kinase pathway.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neurotrophic factor deprivation induces apoptosis, a programmed cell death process.
- Apoptosis requires new gene expression and protein synthesis.
- Understanding the molecular mechanisms of neuronal apoptosis is crucial for neurodegenerative disease research.
Purpose of the Study:
- To identify specific messenger RNAs (mRNAs) expressed during apoptosis.
- To investigate the role of Monoamine Oxidase (MAO) in neuronal cell death.
- To elucidate the involvement of the p38 mitogen-activated protein (MAP) kinase pathway in apoptosis.
Main Methods:
- Subtractive hybridization was employed to identify differentially expressed mRNAs.
- cDNA was prepared from neuronal pheochromocytoma cells undergoing apoptosis.
- Inhibition of p38 MAP kinase pathway and MAO activity were used to assess their roles.
Main Results:
- Monoamine Oxidase (MAO) expression was significantly increased in cells undergoing nerve growth factor withdrawal-induced apoptosis.
- Inhibition of the p38 MAP kinase pathway prevented both increased apoptosis and MAO induction.
- Inhibition of MAO activity suppressed cell death, suggesting a pro-apoptotic role.
Conclusions:
- MAO is upregulated during neurotrophic factor deprivation-induced apoptosis in neuronal cells.
- The p38 MAP kinase pathway mediates the induction of MAO and subsequent apoptosis.
- MAO is a potential downstream target of the p38 MAP kinase pathway in the apoptotic cascade.