Increased glutaredoxin-1 and decreased protein S-glutathionylation in sputum of asthmatics.

GSH, with its redox cycle partners, serves to maintain the reduced state of protein thiols, which can be achieved by scavenging oxidants or by the covalent reversible binding of GSH to protein thiols. The latter occurs under physiological conditions, is induced upon mild oxidative stress and is known as S-glutathionylation (PSSG) [2]. PSSG protects targeted thiols from irreversible oxidations and can modulate protein function. Of significant relevance in asthma, SERCA (sarco/ endoplasmic reticulum calcium ATPase) is activated by PSSG, increasing smooth muscle relaxation, and PSSG of the RyR (ryanodine receptor) calcium channel was associated with impaired coupling. With respect to inflammation, nuclear factor-kB and activator protein-1 are negatively affected by PSSG (reviewed in [2]).