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.