Mechanisms involved in the protection of UV-induced protein inactivation by the corneal crystallin ALDH3A1
Mechanisms involved in the protection of UV-induced protein inactivation by the corneal crystallin ALDH3A1
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DOI：
10.1074/jbc.m607546200
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发表时间：
2007-02-16
影响因子：
4.8
通讯作者：
Vasiliou, Vasilis
中科院分区：
文献类型：
--
作者：
Estey, Tia;Cantore, Miriam;Vasiliou, Vasilis
各种证据表明ALDH3A1（醛脱氢酶3A1）在保护角膜免受紫外线诱导的氧化应激方面起着关键的多方面作用。ALDH3A1是一种角膜晶状体蛋白，它被定义为一种为了结构目的而招募到角膜的蛋白质，而不失去其主要功能（即代谢）。虽然ALDH3A1在有毒醛代谢中的主要作用已经被清楚地证明，包括在紫外线诱导的脂质过氧化过程中产生的醛的解毒，但ALDH3A1在角膜中的结构作用仍然难以捉摸。因此，我们研究了ALDH3A1通过伴侣样活性和其他保护机制抑制其他蛋白质的聚集和/或失活，从而维持角膜光学完整性的潜在贡献。我们发现ALDH3A1在接近生理温度时经历了结构转变，形成了一个部分展开的构象，这提示了伴侣蛋白的活性。虽然这种结构转变本身并不与任何保护作用相关，但当与NADP（+）共培养时，ALDH3A1显著降低了4-羟基-2-壬烯醛和丙二醛对葡萄糖-6-磷酸脱氢酶的失活，加强了这种角膜酶在有毒醛解毒中的代谢功能的重要性。大量过量的ALDH3A1也可以保护葡萄糖-6-磷酸脱氢酶免于因直接暴露在UVB光下而失活，这表明ALDH3A1可以保护其他蛋白质免受紫外线的伤害。总的来说，这些数据表明ALDH3A1不仅可以通过活性醛解毒，还可以通过直接吸收紫外线能量来减少蛋白质的失活和/或聚集。本研究首次提供了支持角膜晶体蛋白ALDH3A1作为角膜吸收紫外线成分的结构作用的机制证据。
Various lines of evidence have shown that ALDH3A1 (aldehyde dehydrogenase 3A1) plays a critical and multifaceted role in protecting the cornea from UV-induced oxidative stress. ALDH3A1 is a corneal crystallin, which is defined as a protein recruited into the cornea for structural purposes without losing its primary function (i.e. metabolism). Although the primary role of ALDH3A1 in the metabolism of toxic aldehydes has been clearly demonstrated, including the detoxification of aldehydes produced during UV-induced lipid peroxidation, the structural role of ALDH3A1 in the cornea remains elusive. We therefore examined the potential contribution of ALDH3A1 in maintaining the optical integrity of the cornea by suppressing the aggregation and/or inactivation of other proteins through chaperone-like activity and other protective mechanisms. We found that ALDH3A1 underwent a structural transition near physiological temperatures to form a partially unfolded conformation that is suggestive of chaperone activity. Although this structural transition alone did not correlate with any protection, ALDH3A1 substantially reduced the inactivation of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal and malondialdehyde when co-incubated with NADP(+), reinforcing the importance of the metabolic function of this corneal enzyme in the detoxification of toxic aldehydes. A large excess of ALDH3A1 also protected glucose-6-phosphate dehydrogenase from inactivation because of direct exposure to UVB light, which suggests that ALDH3A1 may shield other proteins from damaging UV rays. Collectively, these data demonstrate that ALDH3A1 can reduce protein inactivation and/or aggregation not only by detoxification of reactive aldehydes but also by directly absorbing UV energy. This study provides for the first time mechanistic evidence supporting the structural role of the corneal crystallin ALDH3A1 as a UV-absorbing constituent of the cornea.