Redox Regulation of Inflammatory Processes Is Enzymatically Controlled

Table 1

Thiol switches in inflammatory signaling processes.

Protein	Thiol/modification	Function	Regulation	Reference
ADAM17	C600, C630, C635, C640: intermolecular disulfides	Linear order of disulfides (C600–630; C635–640): open, flexible structure; Overlaying disulfides (C600–635; C630–640): abrogates membrane binding and substrate recognition	PDI catalyzes the isomerisation from the linear to the overlaying disulfide pattern.	[135, 141]
Ask1	C200, 250: intramolecular disulfide; C250: interaction with Trx1	ASK1 is involved in TLR4 signaling and is involved in TNFα-induced apoptosis. Intramolecular disulfide induces conformational changes within the Trx-binding region.	Trx1 and Grx1 bind to ASK1 and inhibit the kinase; in case of Trx1 proteasomal degradation is induced. Oxidation of Trx1/ Grx1 induces the dissociation of the complex and kinase activation.	[14, 96, 97, 257]
EGFR	C797: sulfenylation	EGFR-mediated signaling; sulfenylation enhances tyrosine kinase activity.	Oxidation by H2O2	[90, 91]
HMGB1	C23, C45, C106: intramolecular disulfide (C23–45),; sulfenylation(C106)	Fully reduced: chemotactic activity; intramolecular disulfide (C23–45), reduced C106: cytokine	Trx1 (Grx1?)	[154, 155, 157]
Myd88	8 Cys residues: (i) intermolecular disulfides; (ii) nitrosylation	Intermolecular disulfides: oligomerisation during TLR signaling	Oxidation by H2O2 (Prx?), Nrx, Trx	[21, 93, 94]
NFκB	C62: (i) glutathionylation; (ii) sulfenylation	Reduced C62: DNA binding and gene expression	Bound in an inactive complex by Trx1 (cytosol), reduction by Trx1, Grx1 (nucleus)	[16, 99, 101]
Src	C245, C487: disulfide formation	Intramolecular disulfide connects SH2 and kinase domain and stabilizes the active conformation of the kinase	Oxidation by H2O2	[88, 89]