title: Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria.
abstract: Rasagiline protects neuronal cells from cell death caused by various lines of insults. Its neuroprotective function is due to suppression of mitochondrial apoptosis signaling and induction of neuroprotective genes, including Bcl-2 and neurotrophic factors. Rasagiline inhibits the mitochondrial membrane permeabilization, an initial stage in apoptosis, but the mechanism has been elusive. In this paper, it was investigated how rasagiline regulates mitochondrial death cascade in apoptosis induced in SH-SY5Y cells by PK11195, a ligand of the outer membrane translocator protein of 18 kDa. Rasagiline prevented release of cytochrome c (Cyt-c), and the following caspase 3 activation, ATP depletion and apoptosis, but did not inhibit the mitochondrial membrane potential collapse, in contrast to Bcl-2 overexpression. Rasagiline stabilized the mitochondrial contact site and suppressed Cyt-c release into cytoplasm, which should be the critical point for the regulation of apoptosis. Monoamine oxidase was not associated with anti-apoptotic activity of rasagiline in PK11195-induced apoptosis.
authors.affiliation: Department of Neurosciences, Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan, mnaoi@dpc.agu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Naoi
authors.forename: Wakako
authors.initials: W
authors.lastname: Maruyama
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology
chemical_list: D007189:Indans; D007546:Isoquinolines; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C031967:rasagiline; D045304:Cytochromes c; C037850:PK 11195