Persulfidation (S-sulfhydration) and H2S

Abstract

The past decade has witnessed the discovery of hydrogen sulfide (H2S) as a new signalling molecule. Its ability to act as a neurotransmitter, regulator of blood pressure, immunomodulator or anti-apoptotic agent, together with its great pharmacological potential, is now well established. Notwithstanding the growing body of evidence showing the biological roles of H2S, the gap between the macroscopic descriptions and the actual mechanism(s) behind these processes is getting larger. The reactivity towards reactive oxygen and nitrogen species and/or metal centres cannot explain this plethora of biological effects. Therefore, a mechanism involving modification of protein cysteine residues to form protein persulfides is proposed. It is alternatively called S-sulfhydration. Persulfides are not particularly stable and show increased reactivity when compared to free thiols. Detection of protein persulfides is still facing methodological limitations, and mechanisms by which H2S causes this modification are still largely scarce. Persulfidation of protein such as KATP could contribute to H2S-induced vasodilation, while S-sulfhydration of GAPDH and NF-κB inhibits apoptosis. H2S regulates endoplasmic reticulum stress by causing persulfidation of PTP-1B. Several other proteins have been found to be regulated by this posttranslational modification of cysteine. This review article provides a critical overview of the current state of the literature addressing protein S-sulfhydration, with particular emphasis on the challenges and future research directions in this particular field.

Garlic oil polysulfides: H2S- and O2-independent prooxidants in buffer and antioxidants in cells

“…A number of studies have shown that sulfur signaling via regulatory protein cysteines is effectively accomplished by polysulfides through the process of persulfidation (11,20,37,(42)(43)(44). In this process, one (or more?)…”

“…Over 15 proteins have been shown to be regulated via sulfuration, and this number is rapidly increasing (44). However, H 2 S cannot persulfidate protein cysteines because sulfur is in its most reduced form (Ϫ2) as are the reactive protein cysteines, and their reaction is not favored (11,55). In order for H 2 S to persulfidate, either it, or the protein cystine sulfur, must first undergo a two-electron oxidation to sulfane sulfur (0 formal oxidation state), or both must undergo a one-electron oxidation, which is less likely.…”

“…Arguably, the greatest interest in H 2 S and polysulfide signaling is in their ability to bind to a protein cysteine through a process called sulfhydration, or more appropriately persulfidation (11), and, thereby, change the functional properties of that protein (11,19,20,37,44). At least 15 structural proteins or enzymes have been shown to be modified through this process (44), and many of these appear to be proteins that are also activated or inactivated by organosulfur compounds.…”

A potential role of hydrogen sulfide (H2S) in the regulation of the Ras-ERK signaling-dependent transcription of DNA methyltransferases

“…The second reaction is catalyzed by Cystationine-beta-Synthase (CBS) others are catalyzed by Cystathionine-gamma-Lyase (CSE) [5,6].It is now known that H 2 S is a substrate for post-translational modification of a protein, called sulfhydration [7]. Furthermore, H 2 S is an important element of the antioxidant system [8], as well as a regulator of the lipid [9][10][11][12] and NO metabolism [13][14][15][16].…”

“…There is a growing number of studies on the role of protein sulfhydration in the cell signaling [7]. Some of them are dedicated to the Ras-ERK signaling dependence on the sulfhydration, the level of H 2 S concentration and the activity of H 2 S producing enzymes [41][42][43].…”