title: MPP+ induced SH-SY5Y apoptosis is potentiated by cyclosporin A and inhibited by aristolochic acid.
abstract: In experiments investigating the role of the mitochondrial transition pore (MTP) in apoptosis induced by the Parkinsonism producing toxin N-methyl pyridinium ion (MPP+), we attempted to block possible MTP opening with cyclosporin A (CSA) alone or in combination with the phospholipase A2 (PLA2) inhibitor aristolochic acid (ARA). Paradoxically, CSA potentiated rather than inhibited MPP+ induced apoptosis. Aristolochic acid alone inhibited MPP+ induced apoptosis at 24 h but did not alter mitochondrial effects of MPP+, suggesting that ARA inhibits MPP+ induced apoptosis downstream of the initiation event. ARA may prove to be another useful tool for understanding apoptosis.
authors.affiliation: The Neurosciences Graduate Program, The University of Virginia Health Sciences Center, Charlottesville, VA, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Fall
authors.forename: J P
authors.initials: JP
authors.lastname: Bennett
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D034341:Aristolochic Acids; D016572:Cyclosporine / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D014407:Tumor Cells, Cultured
chemical_list: D034341:Aristolochic Acids; D004791:Enzyme Inhibitors; D010616:Phenanthrenes; D016572:Cyclosporine; C000228:aristolochic acid I; D010741:Phospholipases A; D054467:Phospholipases A2; D015655:1-Methyl-4-phenylpyridinium