SIRT3 attenuates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome via autophagy

Sun, Zhengzhu; Fang, Chongfeng; Xu, Shasha; Wang, Bin; Li, Danlei; Liu, Xiaoman; Mi, Yafei; Guo, Hangyuan; Jiang, Jianjun

doi:10.1016/j.bcp.2022.115354

Cited by 21 publications

(6 citation statements)

References 47 publications

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“…Our data provide the first evidence for the protective effect of Sirt3 in the resuscitated heart and the contribution of Sirt3 to the TH-induced maintenance of autophagic flux and subsequent cardioprotection. These findings are consistent with previous research showing that Sirt3 positively regulates myocardial autophagy in metabolic (21), toxic (22,38), and I/R-related (20) cardiomyopathy, and suggest the potential of Sirt3 in the treatment of CA/CPR.…”

Section: Discussionsupporting

confidence: 93%

Sirt3 Mediates the Cardioprotective Effect of Therapeutic Hypothermia After Cardiac Arrest and Resuscitation by Restoring Autophagic Flux via the Pi3k/Akt/Mtor Pathway

Wang,

Xue

et al. 2024

Shock

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Background Postresuscitation cardiac dysfunction is a significant contributor to early death following cardiopulmonary resuscitation (CPR). Therapeutic hypothermia (TH) mitigates myocardial dysfunction due to cardiac arrest (CA); however, the underlying mechanism remains unclear. Sirtuin 3 (Sirt3) was found to affect autophagic activity in recent research, motivating us to investigate its role in the cardioprotective effects of TH in the treatment of CA. Methods Sprague–Dawley rats were used to establish an in vivo CA/CPR model and treated with a selective Sirt3 inhibitor or vehicle. Survival rate, myocardial function, autophagic flux, and Sirt3 expression and activity were evaluated. H9C2 cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. The cells were transfected with Sirt3-siRNA and treated with the autophagy inhibitor chloroquine or the PI3K inhibitor LY294002, and cell viability and autophagic flux were assessed. Results Rats exhibited decreased survival and impaired cardiac function after CA/CPR, which were alleviated by TH. Mechanistically, TH restored Sirt3 expression and autophagic flux which were impaired by CA/CPR. Sirt3 inactivation diminished the capacity of TH to restore autophagic flux and partially abolished the improvements in myocardial function and survival. An in vitro study further showed that TH-induced restoration of disrupted autophagic flux by OGD/R was attenuated by pretreatment with Sirt3-siRNA, and this attenuation was partially rescued by the inhibition of PI3K/Akt/mTOR signaling cascades. Conclusions Sirt3 mediates the cardioprotective effect of TH by restoring autophagic flux via the PI3K/Akt/mTOR pathway. These findings suggest the potential of Sirt3 as a therapeutic target for CA.

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Section: Discussionsupporting

confidence: 93%

Sirt3 Mediates the Cardioprotective Effect of Therapeutic Hypothermia After Cardiac Arrest and Resuscitation by Restoring Autophagic Flux via the Pi3k/Akt/Mtor Pathway

Wang,

Xue

et al. 2024

Shock

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“…For instance, the activation of SIRT1 deacetylates TFEB and FOXOs, thereby promoting autophagolysosomal elimination and preventing DOX-induced cardiac toxicity [ 113 ]. Additionally, SIRT3 activates the mTOR/ULK1 pathway to inhibit NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, restore mitochondrial autophagic flux, and alleviate cardiac toxicity [ 114 ]. Sunitinib, a novel anti-tumor drug, can cause hypertension, left ventricular systolic dysfunction, and myocardial cell death.…”

Section: Role Of Sirtuin-induced Autophagy In Cardiovascular Diseasesmentioning

confidence: 99%

The Current State of Research on Sirtuin-Mediated Autophagy in Cardiovascular Diseases

Wang,

Li,

Ding

et al. 2023

JCDD

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Sirtuins belong to the class III histone deacetylases and possess nicotinamide adenine dinucleotide-dependent deacetylase activity. They are involved in the regulation of multiple signaling pathways implicated in cardiovascular diseases. Autophagy is a crucial adaptive cellular response to stress stimuli. Mounting evidence suggests a strong correlation between Sirtuins and autophagy, potentially involving cross-regulation and crosstalk. Sirtuin-mediated autophagy plays a crucial regulatory role in some cardiovascular diseases, including atherosclerosis, ischemia/reperfusion injury, hypertension, heart failure, diabetic cardiomyopathy, and drug-induced myocardial damage. In this context, we summarize the research advancements pertaining to various Sirtuins involved in autophagy and the molecular mechanisms regulating autophagy. We also elucidate the biological function of Sirtuins across diverse cardiovascular diseases and further discuss the development of novel drugs that regulate Sirtuin-mediated autophagy.

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“…Previous studies showed that activation of mTOR/p70S6K restrained excessive autophagy of granulosa cells (GCs) to mitigate PCOS [ 14 , 17 ]. Moreover, mTOR-mediated autophagy was closely correlated to NLRP3 inflammasome formation and pyroptosis [ 18 , 19 ]. In addition, NLRP3 inflammasome activation was identified to drive ovarian dysfunction and fibrosis in PCOS mice [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/ SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis

Huang,

Li,

Chen

et al. 2024

J Ovarian Res

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Background Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. Methods PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. Results BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. Conclusion Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling.

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SIRT3 attenuates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome via autophagy

Cited by 21 publications

References 47 publications

Sirt3 Mediates the Cardioprotective Effect of Therapeutic Hypothermia After Cardiac Arrest and Resuscitation by Restoring Autophagic Flux via the Pi3k/Akt/Mtor Pathway

Sirt3 Mediates the Cardioprotective Effect of Therapeutic Hypothermia After Cardiac Arrest and Resuscitation by Restoring Autophagic Flux via the Pi3k/Akt/Mtor Pathway

The Current State of Research on Sirtuin-Mediated Autophagy in Cardiovascular Diseases

Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/ SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis

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