S-Thiolation of Protein Sulfhydryls

Abstract

Many cellular proteins have highly reactive sulfhydryls that are especially prone to modification during oxidative stress. Proteins with at least one “reactive” sulfhydryl are prevelant in cytoplasm, membranes, and nuclei, and the concentration of these reactive sites is impressive, reaching or exceeding the concentration of glutathione in many cells. Most proteins contain a single reactive sulfhydryl and are unlikely to form protein-protein disulfides under oxidizing conditions. Therefore, the most likely modification of these single reactive sulfhydryls by oxidative stress is formation of a mixed-disulfide with a low molecular weight cellular thiol such as glutathione, a modification we have termed protein S-thiolation (Ziegler, D.M., 1985 and Grimm, et.al., 1985). (If the modification is known to involve glutathione, the term S-glutathiolation is more descriptive.) This modification is metabolically labile and the rapid “dethiolation” of these proteins by several reductive processes (Park and Thomas, 1989) prevents lasting damage to the protein. Thus, the dynamic modification of proteins by S-thiolation/dethiolation processes represents one of the more important cellular mechanisms for protection against oxidative stress.