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香烟烟雾毒性机制:空气中一氧化氮/异戊二烯混合物对人α-1-蛋白酶抑制剂的失活作用。

Mechanisms of cigarette smoke toxicity: the inactivation of human alpha-1-proteinase inhibitor by nitric oxide/isoprene mixtures in air.

作者信息

Pryor W A, Dooley M M, Church D F

出版信息

Chem Biol Interact. 1985 Jul;54(2):171-83. doi: 10.1016/s0009-2797(85)80161-7.

DOI:10.1016/s0009-2797(85)80161-7
PMID:3875431
Abstract

A mixture of nitric oxide (NO) and isoprene in air has been studied as a model for gas-phase cigarette smoke. We have shown that this model system duplicates many of the properties of cigarette smoke including the inactivation of human alpha-1-proteinase inhibitor (a1PI). In this study, buffered solutions of a1PI were exposed to puffs of air containing 300 ppm NO and 400 ppm isoprene. Bubbling of the NO/air/isoprene gas stream directly through buffered protein solutions causes a1PI to undergo a fast loss of inhibitory capacity. This fast inactivation is not observed when a1PI is exposed to aqueous extracts of the NO/air/isoprene mixture. Both direct exposure and exposure to aqueous extracts, however, cause a1PI to undergo a slow loss of activity that continues for several days as the protein is incubated in the buffer solutions. Gas-phase cigarette smoke has already been shown to cause this same two-phase inactivation of a1PI. The inactivation of a1PI by the model system is dependent on the presence of oxygen in the gas stream, suggesting that the oxidation of nitric oxide to nitrogen dioxide in air is involved in the formation of the inactivating species. The nature of these species remains to be determined; however, small alkoxyl or peroxyl radicals (such as are spin-trappable from gas-phase smoke as well as from the NO/air/isoprene system) do not appear to inactivate a1PI. One possibility is that the inactivating species are metastable compounds formed by radical processes in the gas phase of both cigarette smoke and our model system. Our data suggest that one possible class of species is peroxynitrates.

摘要

已对空气中的一氧化氮(NO)和异戊二烯混合物进行了研究,以此作为气相香烟烟雾的模型。我们已经表明,该模型系统重现了香烟烟雾的许多特性,包括人α-1-蛋白酶抑制剂(a1PI)的失活。在本研究中,将a1PI的缓冲溶液暴露于含有300 ppm NO和400 ppm异戊二烯的空气气流中。使NO/空气/异戊二烯气流直接鼓泡通过缓冲的蛋白质溶液会导致a1PI的抑制能力迅速丧失。当a1PI暴露于NO/空气/异戊二烯混合物的水提取物时,未观察到这种快速失活。然而,直接暴露和暴露于水提取物都会导致a1PI的活性缓慢丧失,随着蛋白质在缓冲溶液中孵育,这种活性丧失会持续数天。气相香烟烟雾已被证明会导致a1PI发生相同的两相失活。模型系统对a1PI的失活取决于气流中氧气的存在,这表明空气中一氧化氮氧化为二氧化氮参与了失活物种的形成。这些物种的性质尚待确定;然而,小的烷氧基或过氧自由基(例如可从气相烟雾以及NO/空气/异戊二烯系统中自旋捕获的自由基)似乎不会使a1PI失活。一种可能性是失活物种是在香烟烟雾和我们的模型系统的气相中通过自由基过程形成的亚稳化合物。我们的数据表明,一类可能的物种是过氧硝酸盐。

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