title: Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: involvement of heat shock protein pathways.
abstract: OBJECTIVE
  We hypothesized that oral l-glutamine supplementations could attenuate muscle damage and oxidative stress, mediated by glutathione (GSH) in high-intensity aerobic exercise by increasing the 70-kDa heat shock proteins (HSP70) and heat shock factor 1 (HSF1).
  
  
  METHODS
  Adult male Wistar rats were 8-week trained (60-min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were supplemented with either l-alanyl-l-glutamine dipeptide (1.5 g/kg, DIP) or a solution containing the amino acids l-glutamine (1g/kg) and l-alanine (0.67 g/kg) in their free form (GLN+ALA) or water (controls).
  
  
  RESULTS
  Plasma from both DIP- and GLN+ALA-treated animals showed higher l-glutamine concentrations and reduced ammonium, malondialdehyde, myoglobin and creatine kinase activity. In the soleus and gastrocnemius muscle of both supplemented groups, l-glutamine and GSH contents were increased and GSH disulfide (GSSG) to GSH ratio was attenuated (p<0.001). In the soleus muscle, cytosolic and nuclear HSP70 and HSF1 were increased by DIP supplementation. GLN+ALA group exhibited higher HSP70 (only in the nucleus) and HSF1 (cytosol and nucleus). In the gastrocnemius muscle, both supplementations were able to increase cytosolic HSP70 and cytosolic and nuclear HSF1.
  
  
  CONCLUSIONS
  In trained rats, oral supplementation with DIP or GLN+ALA solution increased the expression of muscle HSP70, favored muscle l-glutamine/GSH status and improved redox defenses, which attenuate markers of muscle damage, thus improving the beneficial effects of high-intensity exercise training.
authors.affiliation: Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, bloco 14, São Paulo, SP, 05508-900, Brazil.
authors.forename: Eder Ricardo
authors.initials: ER
authors.lastname: Petry
authors.affiliation: Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, bloco 14, São Paulo, SP, 05508-900, Brazil. Electronic address: vinifc@usp.br.
authors.forename: Vinicius Fernandes
authors.initials: VF
authors.lastname: Cruzat
authors.affiliation: Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Regional University of the Northwest of Rio Grande do Sul State, Rio Grande do Sul, Brazil.
authors.forename: Thiago Gomes
authors.initials: TG
authors.lastname: Heck
authors.affiliation: Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, bloco 14, São Paulo, SP, 05508-900, Brazil.
authors.forename: Jaqueline Santos Moreira
authors.initials: JS
authors.lastname: Leite
authors.affiliation: Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Paulo Ivo
authors.initials: PI
authors.lastname: Homem de Bittencourt
authors.affiliation: Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, bloco 14, São Paulo, SP, 05508-900, Brazil.
authors.forename: Julio
authors.initials: J
authors.lastname: Tirapegui
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000502:physiology; D019587:Dietary Supplements; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D005973:Glutamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009211:Myoglobin / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D004151:Dipeptides; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D009211:Myoglobin; D014157:Transcription Factors; D005973:Glutamine; D008315:Malondialdehyde; D003402:Creatine Kinase; D005978:Glutathione; D000409:Alanine; C054122:alanylglutamine
keywords: Exercise; Glutathione; HSF1; HSP70; Oxidative stress