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Cell Mol Life Sci. 2018 Jul;75(13):2321-2337. doi: 10.1007/s00018-018-2806-z. Epub 2018 Mar 28.

Redox-dependent thiol modifications: implications for the release of extracellular vesicles.

Author information

1
Department of Medical Microbiology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
2
Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
3
Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
4
Department of Medical Microbiology and Infection Control, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
5
Medical Clinic I, Department of Respiratory Medicine, Goethe University Hospital, Frankfurt/Main, Germany.
6
Department of Medical Microbiology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. f.stassen@maastrichtuniversity.nl.

Abstract

Extracellular vesicles (EVs), including microvesicles and exosomes, are emerging as important regulators of homeostasis and pathophysiology. During pro-inflammatory and pro-oxidant conditions, EV release is induced. As EVs released under such conditions often exert pro-inflammatory and procoagulant effects, they may actively promote the pathogenesis of chronic diseases. There is evidence that thiol group-containing antioxidants can prevent EV induction by pro-inflammatory and oxidative stimuli, likely by protecting protein thiols of the EV-secreting cells from oxidation. As the redox state of protein thiols greatly impacts three-dimensional protein structure and, consequently, function, redox modifications of protein thiols may directly modulate EV release in response to changes in the cell's redox environment. In this review article, we discuss targets of redox-dependent thiol modifications that are known or expected to be involved in the regulation of EV release, namely redox-sensitive calcium channels, N-ethylmaleimide sensitive factor, protein disulfide isomerase, phospholipid flippases, actin filaments, calpains and cell surface-exposed thiols. Thiol protection is proposed as a strategy for preventing detrimental changes in EV signaling in response to inflammation and oxidative stress. Identification of the thiol-containing proteins that modulate EV release in pro-oxidant environments could provide a rationale for broad application of thiol group-containing antioxidants in chronic inflammatory diseases.

KEYWORDS:

Chronic inflammation; Exosomes; Microvesicles; N-acetyl-L-cysteine; Redox environment; Sulfhydryl groups

PMID:
29594387
PMCID:
PMC5986851
DOI:
10.1007/s00018-018-2806-z
[Indexed for MEDLINE]
Free PMC Article

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