Effect of oxygen concentration on free radical-induced cytotoxicity.
Free radicals induce oxidative stress in vivo, leading to various disorders and diseases. In the present study, the effect of oxygen pressure on the cytotoxicity induced by free radicals was studied. It was found that alkyl radicals markedly aggravated Jurkat cell apoptosis under low oxygen pressure and this was ascribed to a hypoxic condition caused by the consumption of oxygen by alkyl radicals giving peroxyl radicals and subsequent lipid peroxidation by a chain mechanism. The intracellular lipid hydroperoxides significantly increased at an early time point even under hypoxia. Cytochrome c was released from the mitochondria, and caspase-9 as well as caspase-3 was activated during apoptosis, indicating that cell death followed by the intrinsic, mitochondrial apoptosis pathway. Pretreatment with VAD-FMK, a caspase inhibitor, attenuated the apoptosis induced by alkyl radicals under hypoxia. Moreover, pretreatment with various antioxidants also significantly rescued the cells from apoptosis. Taken together, the results indicate that free radicals induced hypoxic conditions, which accelerated mitochondria-dependent cell apoptosis.
Human Stress Signal Research Center, National Institute of Advanced Industrial Science & Technology, Ikeda, Osaka 563-8577, Japan.
Zhi-Hua
ZH
Chen
Yoshiro
Y
Saito
Yasukazu
Y
Yoshida
Etsuo
E
Niki
D000578:Amidines / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D011312:Pressure; D013997:Time Factors
D000578:Amidines; D000975:Antioxidants; D005609:Free Radicals; C046728:2,2'-azobis(2-amidinopropane); D020169:Caspases; D010100:Oxygen