Melatonin Alleviates Cardiac Dysfunction Via Increasing Sirt1-Mediated Beclin-1 Deacetylation and Autophagy During Sepsis.
Inflammation
; 44(3): 1184-1193, 2021 Jun.
Article
in En
| MEDLINE
| ID: mdl-33452667
ABSTRACT
Cardiac dysfunction is a major cause leading to multiple organ failure in sepsis. Beclin-1-dependent autophagy has been evidenced to exert protective effects on hearts in sepsis. However, the mechanisms on how Beclin-1 and autophagy are regulated remains enigmatic. To explore the detailed mechanisms controlling Beclin-1-dependent autophagy in septic heart and whether melatonin could protect against sepsis via regulating cardiac autophagy, adult Sprague-Dawley (SD) rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. Rats were intraperitoneally administrated with 30 mg/kg melatonin within 5-min post-CLP surgery. Our data showed that sepsis induced Becline-1 acetylation and inhibited autophagy in hearts, resulting in impaired cardiac function. However, melatonin treatment facilitated Beclin-1 deacetylation and increased autophagy in septic hearts, thus improved cardiac function. Moreover, melatonin increased the expression and activity of Sirtuin 1 (Sirt1), and inhibition of Sirt1 abolished the protective effects of melatonin on Beclin-1 deacetylation and cardiac function. In conclusion, increased Beclin-1 acetylation was involved in impaired autophagy in septic hearts, while melatonin contributed to Beclin-1 deacetylation via Sirt1, leading to improved autophagy and cardiac function in sepsis. Our study sheds light on the important role of Beclin-1 acetylation in regulating autophagy in sepsis and suggests that melatonin is a potential candidate drug for the treatment of sepsis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Protein Processing, Post-Translational
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Ventricular Function, Left
/
Sepsis
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Myocytes, Cardiac
/
Sirtuin 1
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Beclin-1
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Heart Diseases
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Melatonin
Limits:
Animals
Language:
En
Journal:
Inflammation
Year:
2021
Document type:
Article
Affiliation country:
China