title: Pyridoxamine reverts methylglyoxal-induced impairment of survival pathways during heart ischemia.
abstract: OBJECTIVE
  Increased levels of advanced glycation end-products (AGE) and their precursors, such as methylglyoxal (MG), in patients with diabetes may account for impaired response to heart ischemia. Pyridoxamine is a derivate of vitamin B6, which has been shown to reduce AGE formation. Our goal was to assess the role of pyridoxamine in protecting from MG-induced impaired heart response to ischemia.
  
  
  METHODS
  Wistar rats were subjected to MG administration (WM), MG plus pyridoxamine (WMPyr), or no treatment (W). Half of the hearts from each group were submitted to ischemia and the other half were perfused as control. The levels of CEL, Bcl-2, Bax, and total and phosphorylated forms of JNK and Akt were determined.
  
  
  RESULTS
  Methylglyoxal led to higher levels of AGE and AGE receptor (RAGE) than in the W group. During ischemia, MG caused an impairment of survival pathways and Bcl-2/Bax ratio, a marker of apoptosis. Pyridoxamine treatment decreased glycation and restored the activation of JNK and Akt during ischemia. These events were followed by levels of Bcl-2/Bax ratio similar to W group.
  
  
  CONCLUSIONS
  Methylglyoxal-induced AGE accumulation impairs the activation of cell survival pathways during ischemia. Pyridoxamine-induced decrease of glycation inhibited the effects of MG accumulation in the heart, suggesting that it can be of added value to usual diabetic therapy.
authors.affiliation: Laboratory of Physiology, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Basic Research Unit on Cardiology, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Almeida
authors.forename: Daniela
authors.initials: D
authors.lastname: Santos-Silva
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Paulo
authors.initials: P
authors.lastname: Matafome
authors.forename: Joana
authors.initials: J
authors.lastname: Crisóstomo
authors.forename: Cristina
authors.initials: C
authors.lastname: Sena
authors.forename: Lino
authors.initials: L
authors.lastname: Gonçalves
authors.forename: Raquel
authors.initials: R
authors.lastname: Seiça
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011733:Pyridoxamine / Q000494:pharmacology*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: C494828:Bax protein, rat; D017127:Glycation End Products, Advanced; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011733:Pyridoxamine; D011765:Pyruvaldehyde; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases
keywords: AGE; Diabetes; Heart ischemia; Methylglyoxal; Pyridoxamine