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Gene expression of carnosine-related enzymes and transporters in skeletal muscle

Inge Everaert (UGent) , Hélène De Naeyer (UGent) , Youri Taes (UGent) and Wim Derave (UGent)
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Abstract
Chronic oral beta-alanine supplementation can elevate muscle carnosine (beta-alanyl-L-histidine) content and improve high-intensity exercise performance. However, the regulation of muscle carnosine levels is poorly understood. The uptake of the rate-limiting precursor betaalanine and the enzyme catalyzing the dipeptide synthesis are thought to be key steps. The aims of this study were to investigate the expression of possible carnosine-related enzymes and transporters in both human and mouse skeletal muscle in response to carnosine-altering stimuli. Human gastrocnemius lateralis and mouse tibialis anterior muscle samples were subjected to HPLC and qPCR analysis. Mice were subjected to chronic oral supplementation of beta-alanine and carnosine or to orchidectomy (7 and 30 days, with or without testosterone replacement), stimuli known to, respectively, increase and decrease muscle carnosine and anserine. The following carnosine-related enzymes and transporters were expressed in human and/or mouse muscles: carnosine synthase (CARNS), carnosinase- 2 (CNDP2), the carnosine/histidine transporters PHT1 and PHT2, the beta-alanine transporters TauT and PAT1, betaalanine transaminase (ABAT) and histidine decarboxylase (HDC). Six of these genes showed altered expression in the investigated interventions. Orchidectomy led to decreased muscle carnosine content, which was paralleled with decreased TauT expression, whereas CARNS expression was surprisingly increased. Beta-alanine supplementation increased both muscle carnosine content and TauT, CARNS and ABAT expression, suggesting that muscles increase beta-alanine utilization through both dipeptide synthesis (CARNS) and deamination (ABAT) and further oxidation, in conditions of excess availability. Collectively, these data show that muscle carnosine homeostasis is regulated by nutritional and hormonal stimuli in a complex interplay between related transporters and enzymes.
Keywords
HUMAN VASTUS LATERALIS, BETA-ALANINE SUPPLEMENTATION, Testosterone, Beta-alanine supplementation, Orchidectomy, Beta-alanine aminotransferase, ANSERINE, HUMANS, GENDER, AMINO-ACID, EXERCISE, IDENTIFICATION, CAPACITY, METABOLISM

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Citation

Please use this url to cite or link to this publication:

Chicago
Everaert, Inge, Hélène De Naeyer, Youri Taes, and Wim Derave. 2013. “Gene Expression of Carnosine-related Enzymes and Transporters in Skeletal Muscle.” European Journal of Applied Physiology 113 (5): 1169–1179.
APA
Everaert, I., De Naeyer, H., Taes, Y., & Derave, W. (2013). Gene expression of carnosine-related enzymes and transporters in skeletal muscle. EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY, 113(5), 1169–1179.
Vancouver
1.
Everaert I, De Naeyer H, Taes Y, Derave W. Gene expression of carnosine-related enzymes and transporters in skeletal muscle. EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY. 2013;113(5):1169–79.
MLA
Everaert, Inge, Hélène De Naeyer, Youri Taes, et al. “Gene Expression of Carnosine-related Enzymes and Transporters in Skeletal Muscle.” EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY 113.5 (2013): 1169–1179. Print.
@article{3136649,
  abstract     = {Chronic oral beta-alanine supplementation can elevate muscle carnosine (beta-alanyl-L-histidine) content and improve high-intensity exercise performance. However, the regulation of muscle carnosine levels is poorly understood. The uptake of the rate-limiting precursor betaalanine and the enzyme catalyzing the dipeptide synthesis are thought to be key steps. The aims of this study were to investigate the expression of possible carnosine-related enzymes and transporters in both human and mouse skeletal muscle in response to carnosine-altering stimuli. Human gastrocnemius lateralis and mouse tibialis anterior muscle samples were subjected to HPLC and qPCR analysis. Mice were subjected to chronic oral supplementation of beta-alanine and carnosine or to orchidectomy (7 and 30 days, with or without testosterone replacement), stimuli known to, respectively, increase and decrease muscle carnosine and anserine. The following carnosine-related enzymes and transporters were expressed in human and/or mouse muscles: carnosine synthase (CARNS), carnosinase- 2 (CNDP2), the carnosine/histidine transporters PHT1 and PHT2, the beta-alanine transporters TauT and PAT1, betaalanine transaminase (ABAT) and histidine decarboxylase (HDC). Six of these genes showed altered expression in the investigated interventions. Orchidectomy led to decreased muscle carnosine content, which was paralleled with decreased TauT expression, whereas CARNS expression was surprisingly increased. Beta-alanine supplementation increased both muscle carnosine content and TauT, CARNS and ABAT expression, suggesting that muscles increase beta-alanine utilization through both dipeptide synthesis (CARNS) and deamination (ABAT) and further oxidation, in conditions of excess availability. Collectively, these data show that muscle carnosine homeostasis is regulated by nutritional and hormonal stimuli in a complex interplay between related transporters and enzymes.},
  author       = {Everaert, Inge and De Naeyer, H{\'e}l{\`e}ne and Taes, Youri and Derave, Wim},
  issn         = {1439-6319},
  journal      = {EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY},
  language     = {eng},
  number       = {5},
  pages        = {1169--1179},
  title        = {Gene expression of carnosine-related enzymes and transporters in skeletal muscle},
  url          = {http://dx.doi.org/10.1007/s00421-012-2540-4},
  volume       = {113},
  year         = {2013},
}

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