超氧阴离子:致癌性活性氧物种?

Superoxide anion: oncogenic reactive oxygen species?

作者信息

Pervaiz Shazib, Clement Marie-Veronique

机构信息

Cancer Biology Program, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

出版信息

Int J Biochem Cell Biol. 2007;39(7-8):1297-304. doi: 10.1016/j.biocel.2007.04.007. Epub 2007 Apr 21.

Abstract

Recent evidence linking intracellular reactive oxygen species to cell survival and/or proliferation signals has resulted in a paradigm shift from the age-old dogma implicating reactive oxygen species exclusively in cell damage and death. It is now accepted that reactive oxygen species play important roles in normal physiological states and that depending on the species involved the effect could be highly varied. In this regard, the effects of the two major reactive oxygen species, superoxide and hydrogen peroxide have been extensively studied. During normal cell growth a tight balance between the two species is kept under check by the cells' anti-oxidant defense systems. Deficiency or defect in this defense armory is invariably associated with neoplasia, thus rendering the intracellular redox status in a state of imbalance and generating a "pro-oxidant" milieu. A variety of model systems have underscored the relationship between a pro-oxidant state and cancer promotion and progression. In this review, we present evidence to support the hypothesis that the effect of intracellular reactive oxygen species on oncogenesis is dependent on the ratio of intracellular superoxide to hydrogen peroxide in that a predominant increase in superoxide supports cell survival and promotes oncogenesis whereas a tilt in favor of hydrogen peroxide prevents carcinogenesis by facilitating cell death signaling.

摘要

最近,有关细胞内活性氧与细胞存活和/或增殖信号相关的证据,引发了一种范式转变,即从长期以来认为活性氧仅与细胞损伤和死亡有关的教条中脱离出来。现在人们已经认识到,活性氧在正常生理状态中发挥着重要作用,并且根据所涉及的种类不同,其影响可能差异很大。在这方面,两种主要的活性氧——超氧化物和过氧化氢的影响已得到广泛研究。在正常细胞生长过程中,细胞的抗氧化防御系统会维持这两种物质之间的紧密平衡。这种防御机制的缺陷或不足总是与肿瘤形成相关,从而使细胞内的氧化还原状态失衡,并产生“促氧化剂”环境。各种模型系统都强调了促氧化剂状态与癌症发生和发展之间的关系。在这篇综述中,我们提供证据支持以下假设:细胞内活性氧对肿瘤发生的影响取决于细胞内超氧化物与过氧化氢的比例,即超氧化物的显著增加会支持细胞存活并促进肿瘤发生,而过氧化氢占优势则通过促进细胞死亡信号传导来预防癌症发生。

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