title: Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart.
abstract: SUR2A is an ATP-binding protein that serves as a regulatory subunit of cardioprotective ATP-sensitive K(+) (K(ATP) ) channels. Based on signalling pathway regulating SUR2A expression and SUR2A role in regulating numbers of fully assembled K(ATP) channels, we have suggested that nicotinamide-rich diet could improve physical endurance by stimulating SUR2A expression. We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A. Transgenic mice with solely overexpressed SUR2A on control diet had increased physical endurance in a similar manner as the wild-type mice on nicotinamide-rich diet. 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. In contrast, the same challenge in the wild-type was characterized by a lack of the channel activation and rise in intracellular Ca(2+) . Nicotinamide-rich diet was ineffective to increase physical endurance in mice lacking K(ATP) channels. This study has shown that nicotinamide-rich diet improves physical endurance by increasing expression of SUR2A and that this is a sole mechanism of the nicotinamide-rich diet effect. 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.
authors: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.
authors: Andriy
authors: A
authors: Sukhodub
authors: Rajni
authors: R
authors: Sudhir
authors: Qingyou
authors: Q
authors: Du
authors: Sofija
authors: S
authors: Jovanović
authors: Santiago
authors: S
authors: Reyes
authors: Aleksandar
authors: A
authors: Jovanović
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004032:Diet; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors; D015854:Up-Regulation / Q000187:drug effects; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D000318:Adrenergic beta-Agonists; D002118:Calcium; D007545:Isoproterenol; D009536:Niacinamide; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014803:Vitamin B Complex; D000099161:Kcnj11 Channel; C577511:Abcc9 protein, mouse