Sirtuins and the circadian clock interplay in cardioprotection: focus on sirtuin 1

Soni, Sanjeev Kumar; Basu, Priyoneel; Singaravel, Muniyandi; Sharma, Ramaswamy; Pandi‐Perumal, Seithikurippu R.; Cardinali, Daniel P.; Reíter, Russel J.

doi:10.1007/s00018-020-03713-6

Cited by 34 publications

(25 citation statements)

References 150 publications

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“…The role of proteins of cellular redox homeostasis in cellular timekeeping is emerging [ 41 ], supported by the daytime-dependence of thioredoxin-like protein 1 (TXNL1), glutathione reductase (GSHR) and mercaptopyruvate sulfurtransferase (THTM) protein, shown in our work. In view of involvement of sirtuins in circadian rhythms [ 42 ], the thiamine-dependent correlations between expression of SIRT2 and expression of proteins of the thiol/disulfide metabolism—such as ERO1A, THTM (in the brain of both control and thiamine-treated rats); and PDIA3, PDIA6, GSHR, and TRXR1 (in the brain of thiamine-treated rats) ( Table 2 )—are in good accord with the metabolic significance of the interplay between the protein acetylation and disulfide bonds formation, exemplified, in particular, by the regulation of SIRT2 through S-glutathionylation [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293

Aleshin

Artiukhov

Kaehne

et al. 2021

IJMS

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Coupling glycolysis and mitochondrial tricarboxylic acid cycle, pyruvate dehydrogenase (PDH) complex (PDHC) is highly responsive to cellular demands through multiple mechanisms, including PDH phosphorylation. PDHC also produces acetyl-CoA for protein acetylation involved in circadian regulation of metabolism. Thiamine (vitamin B1) diphosphate (ThDP) is known to activate PDH as both coenzyme and inhibitor of the PDH inactivating kinases. Molecular mechanisms integrating the function of thiamine-dependent PDHC into general redox metabolism, underlie physiological fitness of a cell or an organism. Here, we characterize the daytime- and thiamine-dependent changes in the rat brain PDHC function, expression and phosphorylation, assessing their impact on protein acetylation and metabolic regulation. Morning administration of thiamine significantly downregulates both the PDH phosphorylation at Ser293 and SIRT3 protein level, the effects not observed upon the evening administration. This action of thiamine nullifies the daytime-dependent changes in the brain PDHC activity and mitochondrial acetylation, inducing diurnal difference in the cytosolic acetylation and acetylation of total brain proteins. Screening the daytime dependence of central metabolic enzymes and proteins of thiol/disulfide metabolism reveals that thiamine also cancels daily changes in the malate dehydrogenase activity, opposite to those of the PDHC activity. Correlation analysis indicates that thiamine abrogates the strong positive correlation between the total acetylation of the brain proteins and PDHC function. Simultaneously, thiamine heightens interplay between the expression of PDHC components and total acetylation or SIRT2 protein level. These thiamine effects on the brain acetylation system change metabolic impact of acetylation. The changes are exemplified by the thiamine enhancement of the SIRT2 correlations with metabolic enzymes and proteins of thiol-disulfide metabolism. Thus, we show the daytime- and thiamine-dependent changes in the function and phosphorylation of brain PDHC, contributing to regulation of the brain acetylation system and redox metabolism. The daytime-dependent action of thiamine on PDHC and SIRT3 may be of therapeutic significance in correcting perturbed diurnal regulation.

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Section: Discussionmentioning

confidence: 99%

Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293

Aleshin

Artiukhov

Kaehne

et al. 2021

IJMS

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“…In the kidneys, SIRT1 deacetylates target proteins to inhibit renal inflammation and fibrosis via multiple signal pathways [ 34 ]. Accumulating evidence has demonstrated that SIRT1 regulates blood pressure, glucose-lipid metabolism, and sodium balance [ 35 – 37 ], which also played an important role in kidney diseases. Accordingly, the activation of SIRT1 in the kidney may be a new therapeutic target to rectify independent risk factors of renal diseases, especially OBH renal damage.…”

Section: Discussionmentioning

confidence: 99%

Huoxue Qianyang Qutan Recipe Protects against Early Renal Damage Induced by Obesity-Related Hypertension via the SIRT1/NF-κB/IL-6 Pathway: Integrating Network Pharmacology and Experimental Validation-Based Strategy

Wang

Gui

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Obesity is recognized as not only a major contributing factor to cardiovascular diseases but also an independent risk factor for end-stage renal disease. Previous studies have found that Huoxue Qianyang Qutan Recipe (HQQR) could reduce urinary microalbumin in patients with obesity-related hypertension (OBH). However, the renal protective activity of HQQR in OBH and its molecular targets involved remains ambiguous. In this work, we investigate the mechanism of HQQR against OBH-induced early renal damage using integrating network pharmacology and experimental validation-based strategy. First, via network pharmacology, IL-6 is identified as one of the key targets of HQQR against early renal damage in hypertension, and inhibition of inflammation is a crucial process. Second, in in vivo experiments, HQQR can lower blood pressure, lose weight, and restore metabolic abnormalities in OBH rats, which could be associated with the effects on protecting early renal damage. Finally, in the mechanism, HQQR increases SIRT1 mRNA and protein expression consistent with reduction of NF-κB acetylation and suppressed the p65-mediated inflammatory signaling pathway. As a result, HQQR robustly inhibits OBH-induced renal inflammation by reducing IL-6 mRNA and protein levels in the renal tissue and the release of IL-6 in serum of OBH rats. This study aims to provide a multimethod (network pharmacology-animal experiment) and multilevel (component-target-pathway) strategy for the prevention and treatment of OBH-induced target organ damage by traditional Chinese medicine.

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“…SIRT1, another sirtuin family member, is expressed widely in tissues, and is located in both the nucleus and cytoplasm of adult cardiomyocytes [45]. By deacetylating histone and non-histone proteins, SIRT1 acts as a multifunctional protein that regulates various biological processes, including heart development, autophagy, apoptosis, circadian clock, and lifespan [46], as well as cardiac electrical activity [47]; further, it can protect the heart against myocardial ischemia/reperfusion injury [48]. DOX inhibits the expression of SIRT1.…”

Section: Dox Accumulates In the Mitochondria And Perturbs Mitochondri...mentioning

confidence: 99%

Mitochondrial-Targeted Therapy for Doxorubicin-Induced Cardiotoxicity

Leung

Poon

2022

IJMS

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Anthracyclines, such as doxorubicin, are effective chemotherapeutic agents for the treatment of cancer, but their clinical use is associated with severe and potentially life-threatening cardiotoxicity. Despite decades of research, treatment options remain limited. The mitochondria is commonly considered to be the main target of doxorubicin and mitochondrial dysfunction is the hallmark of doxorubicin-induced cardiotoxicity. Here, we review the pathogenic mechanisms of doxorubicin-induced cardiotoxicity and present an update on cardioprotective strategies for this disorder. Specifically, we focus on strategies that can protect the mitochondria and cover different therapeutic modalities encompassing small molecules, post-transcriptional regulators, and mitochondrial transfer. We also discuss the shortcomings of existing models of doxorubicin-induced cardiotoxicity and explore advances in the use of human pluripotent stem cell derived cardiomyocytes as a platform to facilitate the identification of novel treatments against this disorder.

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Sirtuins and the circadian clock interplay in cardioprotection: focus on sirtuin 1

Cited by 34 publications

References 150 publications

Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293

Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293

Huoxue Qianyang Qutan Recipe Protects against Early Renal Damage Induced by Obesity-Related Hypertension via the SIRT1/NF-κB/IL-6 Pathway: Integrating Network Pharmacology and Experimental Validation-Based Strategy

Mitochondrial-Targeted Therapy for Doxorubicin-Induced Cardiotoxicity

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