Differential effect of nitrogen species on changes in mitochondrial membrane permeability due to mitomycin c in lung epithelial cells.
The effect of reactive nitrogen species (RNS) against the cytotoxicity of mitomycin c (MMC) in lung epithelial cells was assessed by measuring the effect on mitochondrial membrane permeability. RNS had a differential effect against cytotoxicity of MMC depending on concentration. Viability loss in cells exposed to MMC was decreased by inhibitors of caspase-3, -8 and -9 and attenuated by antioxidants (N-acetylcysteine, dithiothreitol, ascorbate and rutin). Addition of 3-morpholinosydnonimine (SIN-1) differentially affected the MMC-induced cell death and GSH depletion concentration dependently with a maximal inhibitory effect at 150 microM. Ascorbate, superoxide dismutase and haemoglobin prevented the inhibitory effect of 150 microM SIN-1 on 10 microg/ml MMC-induced cell death. SIN-1 inhibited the MMC-induced nuclear damage, loss in mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, caspase-3 activation, increase in reactive oxygen species (ROS) formation and depletion of GSH. SIN-1 also attenuated cell death due to H(2)O(2). The cytotoxicity of MMC in the presence of oxidants or RNS producers was much less than the sum of the each effect of MMC and producer. SIN-1 may inhibit the MMC-induced viability loss in lung epithelial cells by suppressing the mitochondrial membrane permeability change and by interaction of its products with MMC.
Park
Se Young
SY
Department of Pharmacology, College of Medicine, Chung-Ang University, 156-756 Seoul, South Korea.
Ko
Hyun Hee
HH
Song
Jin Ho
JH
Han
Eun Sook
ES
Lee
Chung Soo
CS
D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016685:Mitomycin / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D026361:Reactive Nitrogen Species; D016685:Mitomycin