title: 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: Department of Neurosciences, Gifu International Institute of Biotechnology, 1-1 Nakafudogaoka, Kakamigahara, Gifu, 504-0838, Japan.
authors: Keiko
authors: K
authors: Inaba-Hasegawa
authors: Yukihiro
authors: Y
authors: Akao
authors: Wakako
authors: W
authors: Maruyama
authors: Makoto
authors: M
authors: Naoi
mesh_terms: D000704:Analysis of Variance; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D010080:Oxazoles / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C031967:rasagiline; D003609:Dactinomycin; D012642:Selegiline; C090014:befloxatone; D003513:Cycloheximide; D008995:Monoamine Oxidase