title: An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic bcl-2 in human dopaminergic SH-SY5Y cells.
abstract: N-Propargyl-1(R)-aminoindan (rasagiline) is now under phase III clinical trials for Parkinson's disease (PD), and it rescues dopamine neurons from cell death in animal and cellular models of PD. Recently, we proved that rasagiline protected dopaminergic SH-SY5Y cells against apoptosis induced by a dopaminergic neurotoxin, N-methyl(R)salsolinol, and the mechanism was clarified to be due to suppression of death signal transduction in mitochondria. In this paper, the effects of rasagiline on the levels of anti-apoptotic bcl-2 gene family were studied. Rasagiline increased the levels of bcl-2 and bcl-x(l) mRNA at 100-10 nM and 100-10 pM, but not the level of pro-apoptotic bax mRNA. Enhanced expression of bcl-2 family indicates the ability of rasagiline to adjust the apoptotic threshold and protect degenerating neurons in PD.
authors.affiliation: Gifu International Institute of Biotechnology, Mitake, Kani-gun, Gifu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.forename: Wakako
authors.initials: W
authors.lastname: Maruyama
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Masayo
authors.initials: M
authors.lastname: Shamoto-Nagai
authors.forename: Moussa B H
authors.initials: MB
authors.lastname: Youdim
authors.forename: Makoto
authors.initials: M
authors.lastname: Naoi
mesh_terms: D000978:Antiparkinson Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D000978:Antiparkinson Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D007189:Indans; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C031967:rasagiline; D004298:Dopamine