Dalle-Donne Isabella, Milzani Aldo, Gagliano Nicoletta, Colombo Roberto, Giustarini Daniela, Rossi Ranieri
Department of Biology, University of Milan, Milan, Italy.
Antioxid Redox Signal. 2008 Mar;10(3):445-73. doi: 10.1089/ars.2007.1716.
Protein S-glutathionylation, the reversible binding of glutathione to protein thiols (PSH), is involved in protein redox regulation, storage of glutathione, and protection of PSH from irreversible oxidation. S-Glutathionylated protein (PSSG) can result from thiol/disulfide exchange between PSH and GSSG or PSSG; direct interaction between partially oxidized PSH and GSH; reactions between PSH and S-nitrosothiols, oxidized forms of GSH, or glutathione thiyl radical. Indeed, thiol/disulfide exchange is an unlikely intracellular mechanism for S-glutathionylation, because of the redox potential of most Cys residues and the GSSG export by most cells as a protective mechanism against oxidative stress. S-Glutathionylation can be reversed, following restoration of a reducing GSH/GSSG ratio, in an enzyme-dependent or -independent manner. Currently, definite evidence of protein S-glutathionylation has been clearly demonstrated in few human diseases. In aging human lenses, protein S-glutathionylation increases; during cataractogenesis, some of lens proteins, including alpha- and beta-crystallins, form both mixed disulfides and disulfide-cross-linked aggregates, which increase with cataract severity. The correlation of lens nuclear color and opalescence intensity with protein S-glutathionylation indicates that protein-thiol mixed disulfides may play an important role in cataractogenesis and development of brunescence in human lenses. Recently, specific PSSG have been identified in the inferior parietal lobule in Alzheimer's disease. However, much investigation is needed to clarify the actual involvement of protein S-glutathionylation in many human diseases.
蛋白质S-谷胱甘肽化作用，即谷胱甘肽与蛋白质硫醇（PSH）的可逆结合，参与蛋白质氧化还原调节、谷胱甘肽储存以及保护蛋白质硫醇免受不可逆氧化。S-谷胱甘肽化蛋白质（PSSG）可由PSH与GSSG或PSSG之间的硫醇/二硫键交换产生；部分氧化的PSH与GSH之间的直接相互作用；PSH与S-亚硝基硫醇、GSH的氧化形式或谷胱甘肽硫自由基之间的反应。实际上，硫醇/二硫键交换不太可能是细胞内S-谷胱甘肽化的机制，因为大多数半胱氨酸残基的氧化还原电位以及大多数细胞将GSSG输出作为对抗氧化应激的保护机制。随着还原型GSH/GSSG比例的恢复，S-谷胱甘肽化可以通过酶依赖性或非依赖性方式逆转。目前，在少数人类疾病中已明确证明了蛋白质S-谷胱甘肽化的确凿证据。在衰老的人晶状体中，蛋白质S-谷胱甘肽化增加；在白内障形成过程中，一些晶状体蛋白（包括α-和β-晶状体蛋白）形成混合二硫键和二硫键交联聚集体，其随着白内障严重程度的增加而增加。晶状体核颜色和浑浊强度与蛋白质S-谷胱甘肽化的相关性表明，蛋白质-硫醇混合二硫键可能在人晶状体白内障形成和棕色化发展中起重要作用。最近，在阿尔茨海默病的顶下小叶中鉴定出了特定的PSSG。然而，需要进行大量研究以阐明蛋白质S-谷胱甘肽化在许多人类疾病中的实际参与情况。
