Antioxidants (Aug 2019)
Cysteine Glutathionylation Acts as a Redox Switch in Endothelial Cells
Abstract
Oxidative post-translational modifications (oxPTM) of receptors, enzymes, ion channels and transcription factors play an important role in cell signaling. oxPTMs are a key way in which oxidative stress can influence cell behavior during diverse pathological settings such as cardiovascular diseases (CVD), cancer, neurodegeneration and inflammatory response. In addition, changes in oxPTM are likely to be ways in which low level reactive oxygen and nitrogen species (RONS) may contribute to redox signaling, exerting changes in physiological responses including angiogenesis, cardiac remodeling and embryogenesis. Among oxPTM, S-glutathionylation of reactive cysteines emerges as an important regulator of vascular homeostasis by modulating endothelial cell (EC) responses to their local redox environment. This review summarizes the latest findings of S-glutathionylated proteins in major EC pathways, and the functional consequences on vascular pathophysiology. This review highlights the diversity of molecules affected by S-glutathionylation, and the complex consequences on EC function, thereby demonstrating an intricate dual role of RONS-induced S-glutathionylation in maintaining vascular homeostasis and participating in various pathological processes.
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