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

ABSTRACT

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.

KEYWORDS:

• Hydrogen sulfide
• sirtuin-1
• heart failure

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Science and Technology Commission of Shanghai Municipality (22ZR1456900), Shanghai Pujiang Program (2020PJD055).