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Review
. 2022 Apr 20;10(5):1870-1882.
doi: 10.1016/j.gendis.2022.03.022. eCollection 2023 Sep.

Hydrogen sulfide-induced post-translational modification as a potential drug target

Hao-Jie Chen  1   2 , Lei Qian  1   2 , Ke Li  1   2 , Yang-Zhe Qin  1   2 , Jing-Jing Zhou  1   2 , Xin-Ying Ji  1   2   3 , Dong-Dong Wu  1   2   4
Affiliations
Review

Hydrogen sulfide-induced post-translational modification as a potential drug target

Hao-Jie Chen et al. Genes Dis. .

Abstract

Hydrogen sulfide (H2S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H2S has been increasing. H2S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H2S in a variety of physiological processes. Current studies have shown that H2S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H2S on physiological and pathological processes, looking forward to providing guidance for subsequent research.

Keywords: Hydrogen sulfide; Modification; Phosphorylation; S-nitrosylation; S-sulfhydration.

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Figures

Figure 1
Figure 1
The main way of synthesis and metabolism of H2S. Endogenous H2S is mainly produced by three enzyme-catalyzed substrates of CBS, CSE, and 3-MST, and its path mainly includes enzymatic and non-enzymatic degradation. CAT: cysteine aminotransferase; CBS: cystathionine β-synthase; CSE: cystathionine gamma-lyase; DAO: d-amino acid oxidase; 3-MST: 3-mercaptopyruvate sulfurtransferase; PLP: pyridoxal-5-phosphate; SQR: sulfide quinone oxidoreductase system.
Figure 2
Figure 2
The role of different proteins in the cardiovascular system after S-sulfhydration. After protein S-sulfhydration, it exerts anti-oxidative stress in the cardiovascular system, restores ER homeostasis, regulates ion channels, and regulates glucose and lipid metabolism. It plays a role in blood pressure regulation, atherosclerotic plaque formation, and cardiac hypertrophy. CaMKII: Ca2+/calmodulin-dependent protein kinase II; CTSS: cathepsin S; ER: endoplasmic reticulum; ERK1/2: extracellular regulated protein kinase 1/2; HuR: human antigen R; IGF1: insulin-like growth factor-1; IGF1R: insulin-like growth factor-1 receptor; Keap-1: Kelch-like ECH-associated protein1; Kir6.1: ATP-sensitive potassium channel 6.1; KLF5: Krüppel-like factor 5; MEK1: mitogen-activated extracellular signal-regulated kinase 1; MuRF1: muscle RING finger-1; Nrf2: nuclear factor E2-related factor 2; PARP-1: poly (ADP-ribose) polymerase-1; PDI: protein disulphide isomerase; PIP2: phosphatidylinositol (4,5)-bisphosphate; PPARγ：peroxisome proliferator-activated receptor γ; PTP1B: protein tyrosine phosphatase 1B; SP1: specific protein-1; TRPV4 and TRPV1: transient receptor potential family member; VEGFR2: vascular endothelial growth factor receptor 2.
Figure 3
Figure 3
S-sulfhydration plays a role in synapses and participates in memory formation. H2S participates in memory formation through S-sulfhydration of GAPDH, SR, PKA, PKC, and CaMKII, which may all be related to LTP. AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CaMKII: Ca2+/calmodulin-dependent protein kinase II; CBS: cystathionine β-synthase; GluR1: AMPAR subunit; LTP: long-term potentiation; NMDAR: N-methyl-d-aspartate subtype glutamate receptor; PSD95: postsynaptic density 95; Siah: E3 ubiquitin protein ligase; SR: serine racemase.
Figure 4
Figure 4
The role of S-sulfhydration in the kidney. S-sulfhydration regulates ATP production, anti-oxidative stress, regulation of ER stress and water-sodium balance in the kidney. EGFR: endothelial growth factor receptor; ER: endoplasmic reticulum; Keap-1: Kelch-like ECH-associated protein1; Nrf2: nuclear factor E2-related factor 2; Sirt1: silent mating-type information regulator 2 homolog 1.
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