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

Sukhodub A, Sudhir R, Du Q, Jovanović S, Reyes S, Jovanović A - J. Cell. Mol. Med. (2011)

Bottom Line: We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A.The experiments focused on action membrane potential and intracellular Ca(2+) concentration have demonstrated that increased SUR2A expression was associated with the activation of sarcolemmal K(ATP) channels and steady Ca(2+) levels in cardiomyocytes in response to β-adrenergic stimulation.The obtained results suggest that oral nicotinamide is a regulator of SUR2A expression and has a potential as a drug that can improve physical endurance in conditions where this effect would be desirable.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.

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Expression of KATP channel subunits in hearts of mice on control and nicotinamide-rich diet. Representative progress curves for the real-time PCR amplification of SUR2A (A and C) and GAPDH (B and D) cDNA from mice on control or nicotinamide-rich diet (as labelled in the figure) and a corresponding bar graphs (E and F) as well as bar graphs depicting cycle threshold values for Kir6.2 and Kir6.1. Each bar represents mean ± S.E. of the mean (n = 4–6). *P < 0.05.
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fig01: Expression of KATP channel subunits in hearts of mice on control and nicotinamide-rich diet. Representative progress curves for the real-time PCR amplification of SUR2A (A and C) and GAPDH (B and D) cDNA from mice on control or nicotinamide-rich diet (as labelled in the figure) and a corresponding bar graphs (E and F) as well as bar graphs depicting cycle threshold values for Kir6.2 and Kir6.1. Each bar represents mean ± S.E. of the mean (n = 4–6). *P < 0.05.

Mentions: It has been previously shown that the level of SUR2A mRNA correlates well with the number of fully assembled sarcolemmal KATP channels and that this parameter could be used as a proxy measurement of the level of sarcolemmal KATP channels [19, 26–29]. We have analysed levels of SUR2A mRNA as well as mRNAs of two other KATP channel subunits, Kir6.2 and Kir6.1, in mice fed with control and nicotinamide-rich diet. Real time RT-PCR revealed that nicotinamide-rich diet significantly increased the levels of SUR2A mRNA in the heart as the threshold cycle for mice on control and nicotinamide-rich diet was 32.0 ± 0.4 and 22.0 ± 0.9, respectively (n = 6 for each; P < 0.01; Fig. 1). In contrast, no difference was found in mRNA levels of pore-forming KATP channel subunits, Kir6.2 and Kir6.1 (Kir6.2: the threshold cycle was 21.5 ± 0.5 for control and 22.0 ± 0.2 for nicotinamide-rich diet, n = 4, P = 0.35; Kir6.1: 21.2 ± 0.2 for control and 20.7 ± 0.1 for nicotinamide-rich diet, n = 4, P = 0.11; Fig. 1). Also, no significant difference was found in glyceraldehyde 3-phosphate dehydrogenase (GADPH) mRNA levels (Fig. 1; threshold cycle was 14.4 ± 0.2 for mice on control and 13.5 ± 0.8 on nicotinamide-rich diet, n = 6 for each, P = 0.24). As nicotinamide has a similar structure as a KATP channels opener nicorandil, we have tested whether nicotinamide would have any direct effect on KATP channels activity by using perforated patch clamp electrophysiology. Nicotinamide (1 mM) did not have any significant effect on whole cell K+ current in ventricular cardiomyocytes (the current density at 80 mV was 1.84 ± 0.20 pA/pF in the absence and 1.77 ± 0.15 pA/pF in the presence of nicotinamide; n = 4; P = 0.79, Fig. 2A). We have also elucidated possibility that nicotinamide-rich diet affects expression of other subtypes of sulfonylurea receptors (SUR1 and SUR2B) in ventricular tissue as well as expression of SUR1, SUR2A and SUR2B in some non-ventricular tissues. Real time RT-PCR did not reveal any statistically significant differences in level of expression of these subunits between mice on different diets in tested tissues (Fig. 2B).


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

Sukhodub A, Sudhir R, Du Q, Jovanović S, Reyes S, Jovanović A - J. Cell. Mol. Med. (2011)

Expression of KATP channel subunits in hearts of mice on control and nicotinamide-rich diet. Representative progress curves for the real-time PCR amplification of SUR2A (A and C) and GAPDH (B and D) cDNA from mice on control or nicotinamide-rich diet (as labelled in the figure) and a corresponding bar graphs (E and F) as well as bar graphs depicting cycle threshold values for Kir6.2 and Kir6.1. Each bar represents mean ± S.E. of the mean (n = 4–6). *P < 0.05.
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Related In: Results  -  Collection

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fig01: Expression of KATP channel subunits in hearts of mice on control and nicotinamide-rich diet. Representative progress curves for the real-time PCR amplification of SUR2A (A and C) and GAPDH (B and D) cDNA from mice on control or nicotinamide-rich diet (as labelled in the figure) and a corresponding bar graphs (E and F) as well as bar graphs depicting cycle threshold values for Kir6.2 and Kir6.1. Each bar represents mean ± S.E. of the mean (n = 4–6). *P < 0.05.
Mentions: It has been previously shown that the level of SUR2A mRNA correlates well with the number of fully assembled sarcolemmal KATP channels and that this parameter could be used as a proxy measurement of the level of sarcolemmal KATP channels [19, 26–29]. We have analysed levels of SUR2A mRNA as well as mRNAs of two other KATP channel subunits, Kir6.2 and Kir6.1, in mice fed with control and nicotinamide-rich diet. Real time RT-PCR revealed that nicotinamide-rich diet significantly increased the levels of SUR2A mRNA in the heart as the threshold cycle for mice on control and nicotinamide-rich diet was 32.0 ± 0.4 and 22.0 ± 0.9, respectively (n = 6 for each; P < 0.01; Fig. 1). In contrast, no difference was found in mRNA levels of pore-forming KATP channel subunits, Kir6.2 and Kir6.1 (Kir6.2: the threshold cycle was 21.5 ± 0.5 for control and 22.0 ± 0.2 for nicotinamide-rich diet, n = 4, P = 0.35; Kir6.1: 21.2 ± 0.2 for control and 20.7 ± 0.1 for nicotinamide-rich diet, n = 4, P = 0.11; Fig. 1). Also, no significant difference was found in glyceraldehyde 3-phosphate dehydrogenase (GADPH) mRNA levels (Fig. 1; threshold cycle was 14.4 ± 0.2 for mice on control and 13.5 ± 0.8 on nicotinamide-rich diet, n = 6 for each, P = 0.24). As nicotinamide has a similar structure as a KATP channels opener nicorandil, we have tested whether nicotinamide would have any direct effect on KATP channels activity by using perforated patch clamp electrophysiology. Nicotinamide (1 mM) did not have any significant effect on whole cell K+ current in ventricular cardiomyocytes (the current density at 80 mV was 1.84 ± 0.20 pA/pF in the absence and 1.77 ± 0.15 pA/pF in the presence of nicotinamide; n = 4; P = 0.79, Fig. 2A). We have also elucidated possibility that nicotinamide-rich diet affects expression of other subtypes of sulfonylurea receptors (SUR1 and SUR2B) in ventricular tissue as well as expression of SUR1, SUR2A and SUR2B in some non-ventricular tissues. Real time RT-PCR did not reveal any statistically significant differences in level of expression of these subunits between mice on different diets in tested tissues (Fig. 2B).

Bottom Line: We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A.The experiments focused on action membrane potential and intracellular Ca(2+) concentration have demonstrated that increased SUR2A expression was associated with the activation of sarcolemmal K(ATP) channels and steady Ca(2+) levels in cardiomyocytes in response to β-adrenergic stimulation.The obtained results suggest that oral nicotinamide is a regulator of SUR2A expression and has a potential as a drug that can improve physical endurance in conditions where this effect would be desirable.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.

Show MeSH