Leveraging an enzyme/artificial substrate system to enhance cellular persulfides and mitigate neuroinflammation

Abstract

Persulfides and polysulfides, collectively known as the sulfane sulfur pool along with hydrogen sulfide (H2S), play a central role in cellular physiology and disease. Exogenously enhancing these species in cells...

Tetrasulfide bond boosts the anti-tumor efficacy of dimeric prodrug nanoassemblies

“…As a result, the responsivity followed the order of γ-4S-2CTX NPs > γ-3S-2CTX NPs > δ-4S-2CTX NPs > γ-2S-2CTX NPs ( Figure 2 A). Cysteine (Cys), 34 a component of GSH that rendered GSH a potent antioxidant property, triggered the release of drugs from DPNAs in the same way. As shown in Figure 2 B, the CTX release still followed the order of γ-4S-2CTX NPs > γ-3S-2CTX NPs > δ-4S-2CTX NPs > γ-2S-2CTX NPs.…”

“…The ultra-high reduction-responsivity of γ-4S-2CTX NPs can be attributed to three points: (1) both side sulfur and central sulfur of tetrasulfide bond exhibited higher valence orbital electronegativity ( Figure 2 D, bottom right), suggesting they were highly receptive to nucleophilic attack from GSH 30 , 31 ; (2) tetrasulfide bond possessed more sulfur atoms, especially more highly reactive sulfane sulfur 34 , 39 (central sulfur atoms); (3) the reaction of γ-4S-2CTX was accessible to proceed according to the second law of thermodynamics, 29 , 40 due to more H 2 S released in the process significantly increasing the entropy of the system ( Data S4 ).…”

Role of 3-Mercaptopyruvate Sulfurtransferase (3-MST) in Physiology and Disease

“…Transfer of the outer sulfur atom called sulfane sulfur to proteins or small molecule thiol acceptors, resulting in their persulfidation (RS-SH), is deemed responsible for H 2 S signaling mechanisms. A polysulfide species (3-MST-SnSH) is also produced by 3-MST-SSH, and they similarly persulfidate thiols and other proteins [ 30 , 31 , 32 , 33 ].…”

β-Galactosidase-activated nitroxyl (HNO) donors provide insights into redox cross-talk in senescent cells

“…Furthermore, we examine the HNO reaction with H 2 S to produce polysulfides, which are important antioxidants in cells. 14 Additionally, we explore the antioxidant effects of the HNO prodrug in a radiation-induced senescence model.…”