Effect of oxygen concentration on free radical-induced cytotoxicity

Zhi Hua Chen, Yoshiro Saito, Yasukazu Yoshida, Etsuo Niki

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1491-1497
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume72
Issue number6
DOIs
Publication statusPublished - 2008 Jul 1
Externally publishedYes

Keywords

  • Alkyl radicals
  • Apoptosis
  • Cytotoxicity
  • Hypoxia
  • Lipid peroxidation

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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