Thioredoxin 1 regulation of protein -desulfhydration.

The importance of HS in biology and medicine has been widely recognized in recent years, and protein sulfhydration is proposed to mediate the direct actions of HS bioactivity in the body. Thioredoxin 1 (Trx1) is an important reducing enzyme that cleaves disulfides in proteins and acts as an -denitrosylase. The regulation of Trx1 on protein -sulfhydration is unclear. Here we showed that Trx1 facilitates protein -desulfhydration. Overexpression of Trx1 attenuated the basal level and HS-induced protein -sulfhydration by direct interaction with -sulfhydrated proteins, i.e., glyceraldehyde 3-phosphate dehydrogenase and pyruvate carboxylase. In contrast, knockdown of Trx1 mRNA expression by short interfering RNA or blockage of Trx1 redox activity with PX12 or 2,4-dinitrochlorobenzene enhanced protein -sulfhydration. Mutation of cysteine-32 but not cysteine-35 in the Trp-Cys-Gly-Pro-Cys motif eliminated the binding of Trx1 with -sulfhydrated proteins and abolished the -desulfhydrating effect of Trx1. All these data suggest that Trx1 acts as an -desulfhydrase.