Evaluating the Oxidative Stress in Renal Diseases: What Is the Role for S-Glutathionylation?

Abstract

Reactive oxygen species (ROS) have long been considered as toxic derivatives of aerobic metabolism displaying a harmful effect to living cells. Deregulation of redox homeostasis and production of excessive free radicals may contribute to the pathogenesis of kidney diseases. In line, oxidative stress increases in patients with renal dysfunctions due to a general increase of ROS paralleled by impaired antioxidant ability. Emerging evidence revealed that physiologically, ROS can act as signaling molecules interplaying with several transduction pathways such as proliferation, differentiation, and apoptosis. ROS can exert signaling functions by modulating, at different layers, protein oxidation since proteins have "cysteine switches" that can be reversibly reduced or oxidized, supporting the dynamic signaling regulation function. In this scenario, S-glutathionylation is a posttranslational modification involved in oxidative cellular response. Although it is widely accepted that renal dysfunctions are often associated with altered redox signaling, the relative role of S-glutathionylation on the pathogenesis of specific renal diseases remains unclear and needs further investigations. In this review, we discuss the impact of ROS in renal health and diseases and the role of selective S-glutathionylation proteins potentially relevant to renal physiology. The paucity of studies linking the reversible protein glutathionylation with specific renal disorders remains unmet. The growing number of S-glutathionylated proteins indicates that this is a fascinating area of research. In this respect, further studies on the association of reversible glutathionylation with renal diseases, characterized by oxidative stress, may be useful to develop new pharmacological molecules targeting protein S-glutathionylation. Antioxid. Redox Signal. 25, 147-164.