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.
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.
Akao
Yukihiro
Y
Gifu International Institute of Biotechnology, Mitake, Kani-gun, Gifu, Japan.
Maruyama
Wakako
W
Yi
Hong
H
Shamoto-Nagai
Masayo
M
Youdim
Moussa B H
MB
Naoi
Makoto
M
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
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