Reversible and irreversible protein glutathionylation: biological and clinical aspects

• NCJ Number: 308541
• Journal: Expert Opinion on Drug Metabolism & Toxicology Volume: 7 Issue: 7 Dated: 2011 Pages: 891-810
• Author(s): Arthur JL Cooper; John T Pinto; Patrick S Callery
• Date Published: 2011
• Length: 20 pages
• Grant Number(s): 2005-IJ-CX-K014
• Agencies: NIJ-Sponsored
• Publication Type: Research (Applied/Empirical)
• Award: Enhanced Forensic Mass Spectrometry Methods

Annotation

This study examines biological and clinical aspects of reversible and irreversible protein glutathionylation.

Abstract

This article reviews factors contributing to reversible and irreversible protein glutathionylation and their biomedical implications. It also examines the possibility that certain drugs such as busulfan may be toxic by promoting irreversible glutathionylation. The reader will gain an appreciation of the protective nature and control of function resulting from reversible protein glutathionylation. The reader is also introduced to the recently identified phenomenon of irreversible protein glutathionylation and its possible deleterious effects. Depending in part on the glutathione:glutathione disulfide ratio, reversible protein glutathionylation to a mixed disulfide may occur. Reversible glutathionylation is important in protecting proteins against oxidative stress, guiding correct protein folding, regulating protein activity and modulating proteins critical to redox signaling. The potential also exists for irreversible protein glutathionylation via Michael addition of an -SH group to a dehydroalanyl residue, resulting in formation of a stable, non-reducible thioether linkage. The process of reversible protein glutathionylation is now well established but these findings need to be substantiated at the tissue and organ levels, and also with disease state. That being said, irreversible protein glutathionylation can also occur and this has implications in disease and aging. Toxicologists should consider this when evaluating the possible side effects of certain drugs such as busulfan that may generate a glutathionylating species in vivo. (Published Abstract Provided)