title: Protective effect of 1-methylated beta-carbolines against 3-morpholinosydnonimine-induced mitochondrial damage and cell viability loss in PC12 cells.
abstract: The present study investigated the effect of 1-methylated beta-carbolines (harmaline, harmalol and harmine) on change in the mitochondrial membrane permeability and cell death due to reactive nitrogen species in differentiated PC12 cells. beta-Carbolines, caspase inhibitors (z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, dithiothreitol, melatonin, carboxy-PTIO and uric acid) depressed cell viability loss due to 3-morpholinosydnonimine (SIN-1) in PC12 cells. beta-Carbolines inhibited the nuclear damage, the decrease in mitochondrial transmembrane potential, the cytochrome c release, the formation of reactive oxygen species and the depletion of GSH caused by SIN-1 in PC12 cells. beta-Carbolines decreased the SIN-1-induced formations of 3-nitrotyrosine, malondialdehyde and carbonyls in PC12 cells. The results show that 1-methylated beta-carbolines attenuate SIN-1-induced mitochondrial damage. This results in the inhibition of caspase-9 and -3 and apoptotic cell death in PC12 cells by suppressing the toxic actions of reactive oxygen and nitrogen species, including the GSH depletion.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156 756, South Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Choi
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Youn
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Han
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats
chemical_list: D002243:Carbolines; C002385:linsidomine; D008981:Molsidomine