Cystathionine γ-lyase S-sulfhydrates SIRT1 to attenuate myocardial death in isoprenaline-induced heart failure

Objective: Hydrogen sulfide (H2S), the third gasotransmitter, plays a critical role in protecting against heart failure. Sirtuin-1 (SIRT1) is a highly conserved histone deacetylase that has a protective role in the treatment of heart failure by regulating the deacetylation of some functional proteins. This study investigates the interaction between SIRT1 and H2S in heart failure and the underlying mechanisms.Methods and Results: Using endogenous H2S-generating enzyme cystathionine γ-lyase (CSE) knockout mice, we found that CSE deficiency aggravated isoprenaline-induced cardiac injury. Treatment with H2S attenuated atrial natriuretic peptide level, brain natriuretic peptide level, improved cardiac function. Moreover, H2S treatment potentiated myocardial SIRT1 expression. Silencing CSE abolished intracellular SIRT1 expression. Furthermore, CSE/ H2S S-sulfhydrated SIRT1 at its zinc finger domains and augmented its zinc ion binding activity to stabilize the alpha-helix structure.Discussion: In conclusion, these results uncover that a novel mechanism that CSE/H2S S-sulfhydrated SIRT1 to prevent heart dysfunction through modulating its activity.