Hydrogen sulfide stimulates xanthine oxidoreductase conversion to nitrite reductase and formation of NO

Publication date: Available online 30 January 2020Source: Redox BiologyAuthor(s): Sibile Pardue, Gopi K. Kolluru, Xinggui Shen, Sara E. Lewis, Courtney B. Saffle, Eric E. Kelley, Christopher G. KevilAbstractCardiovascular disease is the leading cause of death and disability worldwide with increased oxidative stress, and reduced NO bioavailability serving as a key risk factors. For decades, elevation in protein abundance and enzymatic activity of xanthine oxidoreductase (XOR) under hypoxic/inflammatory conditions has been associated with organ damage and vascular dysfunction. Recent reports have challenged this dogma by identifying a beneficial function for XOR, under similar hypoxic/acidic conditions, whereby XOR catalyzes the reduction of nitrite (NO2-) to nitric oxide (NO) through poorly defined mechanisms. We previously reported that hydrogen sulfide (H2S/sulfide) confers significant vascular benefit under these same conditions via NO2- mediated mechanisms independent of nitric oxide synthase (NOS). Here we report for the first time the convergence of H2S, XOR, and nitrite to form a concerted triad for NO generation. Specifically, hypoxic endothelial cells show a dose-dependent, sulfide and polysulfide (diallyl trisulfide (DATS))-induced, NOS-independent NO2- reduction to NO that is dependent upon the enzymatic activity of XOR. Interestingly, nitrite reduction to NO was found to be slower and more sustained with DATS compared to H2S. Capacity for sulfide/polysulfide to pro...

Source: Redox Biology - January 30, 2020 Category: Biology Source Type: research