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. 2022 Aug 5;20(2):109–125. doi: 10.1038/s41569-022-00741-6

Fig. 2. Sulfide signalling and chemical reaction pathways.

Fig. 2

a | An ischaemia-driven increase in the expression and function of cystathionine γ-lyase (CTH) leads to sulfide metabolite production, which affects both endothelial nitric oxide synthase (eNOS) phosphorylation and hypoxia-inducible factor 1α (HIF1α) activation. This cascade leads to vascular endothelial growth factor (VEGF) and nitric oxide (NO) production, stimulating the monocyte recruitment and endothelial cell (EC) proliferation necessary for angiogenesis and arteriogenesis. b | Sulfide post-translational modifications of eNOS and cGMP-dependent protein kinase 1α (PKG1α), together with electrophilic sulfhydration of 8-nitro-cGMP to 8-SH-cGMP, the soluble guanylate cyclase-β1 subunit (sGCβ1) to sGCβ1 persulfide (sGC-SSH) and phosphodiesterase type 5 (PDE5) to PDE5 persulfide (PDE5-SSH), contribute to increased cGMP levels and subsequent protein kinase G (PKG) activity. c | The effect of sulfide and polysulfide on xanthine oxidase (XO)-dependent nitrite (NO2−) reduction via interaction with either Fe–S clusters or a molybdenum cofactor (Mo-co) domain, which is inhibited by 2,6-dichlorophenolindophenol (DCPIP) or febuxostat, respectively. AKT1, RACα serine–threonine protein kinase; BKCa, large-conductance calcium-activated potassium channel; FGF2, fibroblast growth factor 2; H2S, hydrogen sulfide; KATP, ATP-sensitive potassium channel; Kv7, voltage-gated potassium channels; PI3K, phosphatidylinositol 3-kinase.