Mitochondrial Sirtuin-3 (SIRT3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy by Modulating Protein Acetylation and Oxidative Stress

Circulation Heart Failure, Journal Year: 2022, Volume and Issue: 15(5)

Published: May 1, 2022

Background: High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, hypothesize expression can attenuate induced cardiomyopathy vivo by preventing proteins. Methods: Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), M1-SIRT3 (full-length localized) transgenic mice were treated with 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure function validated immunohistochemistry immunofluorescence (n=4–10). Mass spectrometry on peptides saline (n=6) (n=5) hearts. Validation primary human stem cell derived cardiomyocytes transduced adenoviruses deficient mutants Results: revealed partially resistant changes whereas prevented remodeling dysfunction. In hearts, 37 unique sites proteins altered. Pathway analysis these are involved energy production, fatty acid metabolism, oxidative stress resistance. Increased attenuated doxorubicin-induced superoxide formation, unable prevent stress. Conclusions: Doxorubicin reduced markedly affected acetylome. dysfunction, suggesting could be a potential therapeutic target mitigating

Language: Английский

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FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition

Redox Biology, Journal Year: 2022, Volume and Issue: 58, P. 102530 - 102530

Published: Nov. 15, 2022

Diabetic retinopathy (DR) and other diabetic vascular complications are the leading cause of death disability in patients with suboptimum glycemic control. In pathogenesis diseases, hyperglycemia-induced oxidative stress, DNA damage, poly-ADP-ribose-polymerase (PARP) hyperactivation play important roles endothelial cell impairment. Adipose differentiation-related protein FBXW7 was reported to regulate PGC-1α stability mitochondrial homeostasis. Here, we investigated role mechanism repairing stress injuries under hyperglycemic conditions. promoted hampered activity homologous recombination non-homologues end joining pathway for double-strand breaks an initiating factor PARP complications. The abundant mobilization damage repair mediated by suppressed activation, downregulation expression both human cells rat retinas. This provided a new method inhibition, superior inhibitors treating complication. Furthermore, rescued downregulated NAD+ levels ameliorated dysfunction, thereby reducing superoxide production These effects reversed injury leakage retina, providing potential future treatment strategy.

Language: Английский

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Hypoxia-Inducible Factor 1 and Mitochondria: An Intimate Connection

Biomolecules, Journal Year: 2022, Volume and Issue: 13(1), P. 50 - 50

Published: Dec. 27, 2022

The general objective of the review is to explain interaction between HIF-1 and mitochondria. On one hand, this describes effects on mitochondrial structure, including quantity, distribution, morphology, as well metabolism respiratory function. other various factors, activation enzymes, chain, complex decoupling proteins, affect stability activity HIF-1. It possible develop future molecular therapeutic interventions by understanding interrelationships

Language: Английский

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Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 19, 2022

Sirtuins are a family of nicotinamide adenine dinucleotide (NAD) + -dependent histone deacetylases, comprising seven members SIRT1-SIRT7. have been extensively studied in regulating ageing and age-related diseases. also pivotal modulators oxidative stress inflammation, as they can regulate the expression activation downstream transcriptional factors (such Forkhead box protein O3 (FOXO3a), nuclear factor erythroid 2-related 2 (Nrf2) factor-kappa B (NF-κB)) well antioxidant enzymes, through epigenetic modification post-translational modification. Most importantly, studies shown that aberrant sirtuins involved pathogenesis infectious inflammatory oral diseases, cancer. In this review, we provide comprehensive overview regulatory patterns at multiple levels, essential roles stress, bone metabolism. We summarize involvement several diseases such periodontitis, apical pulpitis, candidiasis, herpesvirus infections, dental fluorosis, At last, discuss potential utilization therapeutic targets

Language: Английский

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Sirtuin 3: Emerging therapeutic target for cardiovascular diseases

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 180, P. 63 - 74

Published: Jan. 11, 2022

Language: Английский

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