Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase.

Abstract

Rasagiline and (-)deprenyl (selegiline), irreversible type B monoamine oxidase (MAO-B) inhibitors, protect neuronal cells through gene induction of pro-survival Bcl-2 and neurotrophic factors in the cellular models of neurodegenerative disorders. In this paper, the role of MAO in the up-regulation of neuroprotective Bcl-2 gene by these inhibitors was studied using type A MAO (MAO-A) expressing wild SH-SY5Y cells and the transfection-enforced MAO-B overexpressed cells. Rasagiline and (-)deprenyl, and also befloxatone, a reversible MAO-A inhibitor, increased Bcl-2 mRNA and protein in SH-SY5Y cells. Silencing MAO-A expression with short interfering (si) RNA suppressed Bcl-2 induction by rasagiline, but not by (-)deprenyl. MAO-B overexpression inhibited Bcl-2 induction by rasagiline and befloxatone, but did not affect that by (-)deprenyl, suggesting the different mechanisms behind Bcl-2 gene induction by these MAO-B inhibitors. The novel role of MAO-A in Bcl-2 induction by rasagiline is discussed with regard to the molecular mechanism underlying neuroprotection by the MAO inhibitors.

• Authors: Keiko Inaba-Hasegawa, Yukihiro Akao, Wakako Maruyama, Makoto Naoi
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 119 Issue 4 Pg. 405-14 (Apr 2012) ISSN: 1435-1463 [Electronic] Austria
• PMID: 22065207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indans
• Monoamine Oxidase Inhibitors
• Oxazoles
• Protein Synthesis Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• RNA, Small Interfering
• rasagiline
• Dactinomycin
• Selegiline
• befloxatone
• Cycloheximide
• Monoamine Oxidase

Topics

• Analysis of Variance
• Cell Line, Tumor
• Cycloheximide (pharmacology)
• Dactinomycin (pharmacology)
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Indans (pharmacology)
• Mitochondria (drug effects, metabolism)
• Monoamine Oxidase (genetics, metabolism)
• Monoamine Oxidase Inhibitors (pharmacology)
• Neuroblastoma (pathology)
• Oxazoles (pharmacology)
• Protein Synthesis Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA Interference (physiology)
• RNA, Messenger (metabolism)
• RNA, Small Interfering (pharmacology)
• Selegiline (pharmacology)
• Transfection
• Up-Regulation (drug effects)