Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart

Sukhodub, Andriy; Sudhir, Rajni; Du, Qingyou; Jovanović, Sofija; Reyes, Santiago; Jovanović, Aleksandar

doi:10.1111/j.1582-4934.2010.01156.x

Cited by 26 publications

(51 citation statements)

References 33 publications

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“…* P \ 0.05 when compared to the wild type. WT wild type expression alone increase the number of K ATP channels (Du et al 2006(Du et al , 2010, increases heart resistance to b-adrenergic stress (Sukhodub et al 2010a) and hypoxia (Sukhodub et al 2010b). In turn, increased heart resistance to metabolic stress leads to improved physical endurance (Sukhodub et al 2010a).…”

Section: Discussionmentioning

confidence: 98%

“…The treadmill endurance test consisted of a step-wise increase in velocity over time at constant incline (as described in Zingman et al 2002;Sukhodub et al 2010a). Inability to continue with physical activity was determined by the animal being unable to continue test irrespective of encouragement by electric shock.…”

Section: Treadmill Testmentioning

confidence: 99%

“…This is believed to be due SUR2A being the least expressed K ATP channel forming protein (Du et al 2006) leading to the phenomenon that the changes of SUR2A levels alone are sufficient for changes in the number of fully assembled K ATP channels (reviewed by Jovanović and Jovanović 2009). Recently, we have found that mice with moderately increased SUR2A mRNA and protein levels are characterized by increased numbers of sarcolemmal K ATP channel in the heart and increased physical resistance (Sukhodub et al 2010a). The underlying mechanism of SUR2A-mediated increase in physical endurance was shown to be associated with increase in number of fully-assembled K ATP channels in cardiomyocytes leading to earlier K ATP channels activation and improved Ca 2?…”

Section: Introductionmentioning

confidence: 98%

“…The underlying mechanism of SUR2A-mediated increase in physical endurance was shown to be associated with increase in number of fully-assembled K ATP channels in cardiomyocytes leading to earlier K ATP channels activation and improved Ca 2? homeostasis in cardiomyocytes in response to b-adrenergic stress (Sukhodub et al 2010a). …”

Section: Introductionmentioning

confidence: 98%

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Ageing-induced decline in physical endurance in mice is associated with decrease in cardiac SUR2A and increase in cardiac susceptibility to metabolic stress: therapeutic prospects for up-regulation of SUR2A

Sudhir

Sukhodub

et al. 2010

Biogerontology

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Ageing is characterized by decline in physical endurance which has been suggested to be partly due to diminished functional and adaptive reserve capacity of the heart. Ageing is associated with decrease in numbers of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels, but whether this has anything to do with ageing-induced decline in physical endurance is yet to be determined. We have previously shown that the numbers of sarcolemmal K(ATP) channels are controlled by the level of expression of SUR2A, a K(ATP) channel regulatory subunit. Here, we have found that ageing decreases the level of SUR2A mRNA in the heart without affecting expression of pore-forming K(ATP) channel subunits, Kir6.1 and Kir6.2. This effect of ageing was associated with decrease in levels of fully-assembled sarcolemmal K(ATP) channels. At the same time, ageing was associated with decreased physical endurance. In order to determine whether increased expression of SUR2A would counteract ageing-induced decrease in physical endurance, we have taken advantage of mice which SUR2A levels are regulated by more efficient CMV promoter. These mice had increased resistance of cardiomyocytes to metabolic stress/hypoxia and increased physical endurance when compared to the wild type. In transgenic mice, ageing did not affect the level of SUR2A mRNA in the heart and the level of fully-assembled sarcolemmal K(ATP) channels. The effect of increased SUR2A to resistance of cardiomyocytes to hypoxia and physical endurance was retained in old mice. The magnitude of these effects was such that they were significantly increased even when compared to those in wild type young mice. We conclude that (1) the level of SUR2A expression in the heart is important factor in regulating physical endurance, (2) ageing-induced decrease in cardiac SUR2A is, at least in part, responsible for ageing-induced decline in physical fitness and (3) up-regulation of SUR2A could be a viable strategy to counteract ageing-induced decline in physical endurance.

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Section: Discussionmentioning

confidence: 98%

Section: Treadmill Testmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

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Ageing-induced decline in physical endurance in mice is associated with decrease in cardiac SUR2A and increase in cardiac susceptibility to metabolic stress: therapeutic prospects for up-regulation of SUR2A

Sudhir

Sukhodub

et al. 2010

Biogerontology

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“…31 Researchers have found that the sole overexpression of the sulfonylurea receptor 2A protein generates a cardiac phenotype with more sarcolemmal K ATP channels, which is essential for preconditioning-induced cardioprotection, thus, increasing resistance to hypoxia and ischemia. [32][33][34][35][36] Therefore, it is possible that the sulfonylurea receptor 2A-mediated pathway that is regulated by Nampt acts assists in SIRT1-related cardioprotection.…”

Section: Upstream Mediators Nicotinamide Phosphoribosyltransferasementioning

confidence: 99%

Novel Role of Silent Information Regulator 1 in Myocardial Ischemia

Yang

Duan

et al. 2013

Circulation

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T he incidence of cardiovascular diseases is increasing at an alarming rate throughout the world. According to the World Health Report 2010, cardiovascular disease accounts for 17.1 million global deaths per year, or 29% of total deaths worldwide. It is predicted that this number will increase to 23.6 million by 2030. Myocardial ischemia, which is reported to induce irreversible damage to the myocardium, causes a number of cardiovascular diseases, such as myocardial infarction, myocardial hypertrophy, atherosclerosis, and heart failure. Medical treatment that effectively prevents ischemic injury would alleviate the consequent development of cardiac remodeling and failure. Previous studies have indicated that ischemic preconditioning (IPC), caloric restriction, resveratrol preconditioning, and some related factors can prevent ischemic injury to the heart and are cardioprotective.1 The underlying mechanisms of these interventions appear to be controlled by a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase called silent information regulator 1 (SIRT1).SIRT1 is a member of the class III group of histone deacetylases, collectively called sirtuins. 2 The mammalian sirtuin family consists of 7 members, designated SIRT1 through SIRT7, which are characterized by a conserved 275-amino-acid catalytic core and unique additional N-terminal and C-terminal sequences of variable length.3 Previous studies have shown that SIRT1 can deacetylate many transcription factors, including forkhead box O (FOXO) transcription factors, p53, nuclear factor-κB (NF-κB), liver X receptor, peroxisome proliferator-activated receptor γ, and brain and muscle Arnt-like protein 1, and nuclear coactivators, as well, including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), cAMP-responsive element-binding protein-regulated transcription coactivator 2, and period homolog 2.4,5 SIRT1 also deacetylates serine/threonine kinase 11, endothelial nitric oxide synthase (eNOS), and histones H1, H3, and H4.2 It has been reported that SIRT1 performs a wide variety of functions in a variety of biological systems, including obesity-associated metabolic diseases, cancer, aging, cellular senescence, cardiac aging and stress, prion-mediated neurodegeneration, inflammation, and placental cell survival. 5 Most importantly, SIRT1 is involved in cardioprotection.Several studies suggest that SIRT1 plays a role in myocardial ischemia. Pillai and colleagues 6 found that SIRT1 was involved in the effect of fructose feeding on myosin heavy chain (MHC) gene expression and cardiac protection. Additionally, the localization of SIRT1 has been reported to change during cardiac development and under stress conditions. 7 Moreover, Sciarretta and colleagues 8 have reported that SIRT1 plays a role in the cardiac autophagy signaling pathway. In these mechanisms, SIRT1 is controlled by several upstream molecules, such as fructose, Longevinex, nicotinamide phosphoribosyltransferase (Nampt), and microRNA (MIR)-199a. Meanwhile, SIRT1 regulates many...

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Improved adaptation to physical stress in mice overexpressing SUR2A is associated with changes in the pattern of Q-T interval

Sudhir

Sukhodub

et al. 2020

Pflugers Arch - Eur J Physiol

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The purpose of this study was to determine whether increased expression of SUR2A, a regulatory subunit of sarcolemmal ATP-sensitive K + (K ATP) channels, improves adaptation to physical stress and regulates cardiac electrophysiology in physical stress. All experiments have been done on transgenic mice in which SUR2A expression was controlled by cytomegalovirus immediate-early (CMV) promoter (SUR2A) and their littermate wild-type controls (WT). The levels of mRNA in heart tissue were measured by real-time RT-PCR. Electrocardiogram (ECG) was monitored with telemetry. The physical adaptation to stress was elucidated using treadmill. We have found that SUR2A mice express 8.34 ± 0.20 times more myocardial SUR2A mRNA than WT (n = 8-18). The tolerated workload on exercise stress test was more than twofold higher in SUR2A than in WT (n = 5-7; P = 0.01). The pattern of Q-T interval from the beginning of the exercise test until drop point was as follows in the wild type: (1) increase in Q-T interval, (2) decrease in Q-T interval, (3) steady stage with a further decrease in Q-T interval, and (4) a sharp increase in Q-T interval. The pattern of Q-T interval was different in transgenic mice and the following stages have been observed: (1) increase in Q-T interval, (2) decrease in Q-T interval, and (3) prolonged steady-state stage with a slight decrease in Q-T interval. In SUR2A mice, no stage 4 (a sharp increase in Q-T interval) was observed. Based on the obtained results, we conclude that an increase in the expression of SUR2A improves adaptation to physical stress and physical endurance by increasing the number of sarcolemmal K ATP channels and, by virtue of their channel activity, improving Ca 2+ homeostasis in the heart.

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Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart

Cited by 26 publications

References 33 publications

Ageing-induced decline in physical endurance in mice is associated with decrease in cardiac SUR2A and increase in cardiac susceptibility to metabolic stress: therapeutic prospects for up-regulation of SUR2A

Ageing-induced decline in physical endurance in mice is associated with decrease in cardiac SUR2A and increase in cardiac susceptibility to metabolic stress: therapeutic prospects for up-regulation of SUR2A

Novel Role of Silent Information Regulator 1 in Myocardial Ischemia

Improved adaptation to physical stress in mice overexpressing SUR2A is associated with changes in the pattern of Q-T interval

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