MECHANISMS OF CELLULAR-RESISTANCE TO HYDROGEN-PEROXIDE, HYPEROXIA, AND 4-HYDROXY-2-NONENAL TOXICITY - THE SIGNIFICANCE OF INCREASED CATALASE ACTIVITY IN H2O2-RESISTANT FIBROBLASTS

被引:83
作者
SPITZ, DR
ADAMS, DT
SHERMAN, CM
ROBERTS, RJ
机构
[1] Department of Pediatrics, Division of Neonatology, University of Virginia, Charlottesville, VA 22908, MR-4
基金
美国国家卫生研究院;
关键词
D O I
10.1016/0003-9861(92)90071-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An H2O2-resistant variant (OC14) of the HA1 Chinese hamster fibroblast cell line which demonstrates a 20-fold increase in catalase activity was utilized in the study of mechanisms responsible for cellular resistance to hydrogen peroxide, oxygen, and 4-hydroxy-2-nonenal toxicity. HA1 and OC14 cells were treated with 9 mm aminotriazole which resulted in a 60 to 80% reduction in catalase activity. Pretreatment with aminotriazole resulted in significant sensitization to the toxicity of 1-h exposures to exogenously applied H2O2, which was proportional to the reduction in catalase activity. Treatment with aminotriazole produced significant sensitization to the toxicity of 95% O2 after 45 h of O2 exposure but no sensitization to the toxicity of a 1-h exposure to 50 μm 4-hydroxy-2-nonenal. Inhibition of catalase activity by aminotriazole had no effect on the metabolism of 4-hydroxy-2-nonenal by either cell line tested. These results support the conclusion that in H2O2-resistant cells, catalase activity is a major determinant of cellular resistance to H2O2 toxicity, whereas catalase activity has a limited role in cellular resistance to an acute exposure to 95% O2 and is unrelated to cellular resistance to 4-hydroxy-2-nonenal. © 1992.
引用
收藏
页码:221 / 227
页数:7
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