Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Peng, Kezheng; Zeng, Chenye; Gao, Yuqi; Liu, Binliang; Li, Liyuan; Xu, Kang; Yin, Yuemiao; Qiu, Ying; Zhang, Mingkui; Ma, Fang; Wang, Zhao

doi:10.1016/j.apsb.2023.03.019

Cited by 8 publications

(2 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 E and Additional file 4 ). Next, we identified the two DeSFGs, named, Sirt2 and Sirt6, among the differentially expressed Sirt family genes, because these two genes have been closely associated with mitophagy and pyroptosis [ 24 – 26 ], especially Sirt6. To understand the relationship between these two DeSFGs and mitophagy or pyroptosis, we constructed an interaction network, as depicted in Fig.…”

Section: Resultsmentioning

confidence: 99%

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

Liu,

Wang,

Wang

et al. 2024

Clin Epigenet

View full text Add to dashboard Cite

Background The management of myocardial ischemia–reperfusion injury (MIRI) presents continuous therapeutic challenges. NAD-dependent deacetylase Sirtuin 6 (Sirt6) plays distinct roles in various disease contexts and is hence investigated for potential therapeutic applications for MIRI. This study aimed to examine the impact of Sirt6-overexpressing exosomes derived from adipose stem cells (S-ASC-Exo) on MIRI, focusing on their influence on AIM2-pyroptosis and mitophagy processes. The sirtuin family of proteins, particularly Sirtuin 6 (Sirt6), play a pivotal role in these processes. This study aimed to explore the potential therapeutic effects of Sirt6-enriched exosomes derived from adipose stem cells (S-ASC-Exo) on regulating MIRI. Results Bioinformatic analysis revealed a significant downregulation of Sirt6 in MIRI subjected to control group, causing a consequential increase in mitophagy and pyroptosis regulator expressions. Therefore, our study revealed that Sirt6-enriched exosomes influenced the progression of MIRI through the regulation of target proteins AIM2 and GSDMD, associated with pyroptosis, and p62 and Beclin-1, related to mitophagy. The introduction of S-ASC-Exo inhibited AIM2-pyroptosis while enhancing mitophagy. Consequently, this led to a significant reduction of GSDMD cleavage and pyroptosis in endothelial cells, catalyzing a deceleration in the progression of atherosclerosis. Extensive in vivo and in vitro assays were performed to validate the expressions of these specific genes and proteins, which affirmed the dynamic modulation by Sirt6-enriched exosomes. Furthermore, treatment with S-ASC-Exo drastically ameliorated cardiac functions and limited infarct size, underlining their cardioprotective attributes. Conclusions Our study underscores the potential therapeutic role of Sirt6-enriched exosomes in managing MIRI. We demonstrated their profound cardioprotective effect, evident in the enhanced cardiac function and attenuated tissue damage, through the strategic modulation of AIM2-pyroptosis and mitophagy. Given the intricate interplay between Sirt6 and the aforementioned processes, a comprehensive understanding of these pathways is essential to fully exploit the therapeutic potential of Sirt6. Altogether, our findings indicate the promise of Sirt6-enriched exosomes as a novel therapeutic strategy in treating ischemia–reperfusion injuries and cardiovascular diseases at large. Future research needs to underscore optimizing the balance of mitophagy during myocardial ischemia to avoid potential loss of normal myocytes.

show abstract

Section: Resultsmentioning

confidence: 99%

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

Liu,

Wang,

Wang

et al. 2024

Clin Epigenet

View full text Add to dashboard Cite

show abstract

“…SIRT6 deletion has been reported to induce the transcriptional activity and DNA binding activity of nuclear factor κB, further exacerbating Ang-II-induced myofibroblast differentiation [ 100 , 112 ]. In addition, SIRT6 has also been shown to enhance mitochondrial biogenesis and mitophagy by deacetylation and inhibition of Sgk1, capable of ameliorating the cardiotoxicity induced by the anthracycline doxorubicin [ 74 ].…”

Section: Fibrosismentioning

confidence: 99%

SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging

Wei,

Li,

Chen

et al. 2024

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Fibrosis is a typical aging-related pathological process involving almost all organs, including the heart, kidney, liver, lung, and skin. Fibrogenesis is a highly orchestrated process defined by sequences of cellular response and molecular signals mechanisms underlying the disease. In pathophysiologic conditions associated with organ fibrosis, a variety of injurious stimuli such as metabolic disorders, epigenetic changes, and aging may induce the progression of fibrosis. Sirtuins protein is a kind of deacetylase which can regulate cell metabolism and participate in a variety of cell physiological functions. In this review, we outline our current understanding of common principles of fibrogenic mechanisms and the functional role of SIRT3/6 in aging-related fibrosis. In addition, sequences of novel protective strategies have been identified directly or indirectly according to these mechanisms. Here, we highlight the role and biological function of SIRT3/6 focus on aging fibrosis, as well as their inhibitors and activators as novel preventative or therapeutic interventions for aging-related tissue fibrosis. Graphical abstract

show abstract

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6

Song,

Yi,

Zeng

et al. 2024

Mol Neurobiol

View full text Add to dashboard Cite

Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Cited by 8 publications

References 63 publications

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers

SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6

Contact Info

Product

Resources

About