Biphasic regulation of hydrogen sulfide in inflammation

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Hydrogen sulfide (H2S),which was formerly recognized as a colorless,toxic gas,was recently reported to be a novel gasotransmitter.Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are the two main H2S-generating enzymes characterized by tissue-specific expression.CSE is predominantly located in the heart.1 Like its two cousins nitric oxide (NO) and carbon monoxide (CO),H2S is a simple inorganic molecule with similar properties,such as rapid diffusion and a short life span.H2S is involved in the multi functional regulation of vasodilation,inflammation,cellular cycle,ischemia/reperfusion,oxidative stress and neuromodulation.Duet al firstly described H2S as a messenger molecule in cardiovascular system.Meanwhile,the role of H2S in inflammation has attracted growing interest in recent years as a large number of experiments have been performed to identify its effect in different animal models with multi-target approaches.Further studies have explored the molecular mechanism of action for H2S including the reaction with disulfide groups and metal ions in proteins to regulate enzymatic functions3 and the interplay between H2S and NO.4,5 To date,DL-propargylglycine (PAG) and NaHS are the two principal chemical entities used in related investigations.PAG,an irreversible inhibitor of the H2S-synthesizing enzyme CSE,is permeable to biomembrane and inhibits CSE activity by blocking substrate cysteine from binding to the active site.NaHS produces H2S in vivo and serves as exogenous H2S donor.
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