Protective effect of 1-methylated beta-carbolines against 3-morpholinosydnonimine-induced mitochondrial damage and cell viability loss in PC12 cells.
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.
Choi
Won Tae
WT
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156 756, South Korea.
Youn
Young Chul
YC
Han
Eun Sook
ES
Lee
Chung Soo
CS
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
D002243:Carbolines; C002385:linsidomine; D008981:Molsidomine