title: Pathways responsible for apoptosis resulting from amadori-induced oxidative and nitrosative stress in human mesothelial cells.
abstract: BACKGROUND
  Apoptosis and inflammatory/oxidative stress have been associated with hyperglycemia in human peritoneal mesothelial cells (HPMCs) and other cell types. We and others have highlighted the role of early products of non-enzymatic protein glycation in inducing proinflammatory conditions and increasing apoptotic rates in HPMCs. Loss of HPMCs seems to be a hallmark of complications associated with peritoneal membrane dysfunction. The aim of this work is to elucidate the mechanisms by which Amadori adducts may act upon HPMC apoptosis.
  
  
  METHODS
  HPMCs isolated from different patients were exposed to different Amadori adducts, i.e. highly glycated hemoglobin (10 nM) and glycated bovine serum albumin (250 μg/ml), to study cell death and several proapoptotic markers by different experimental approaches.
  
  
  RESULTS
  Amadori adducts, but not their respective controls, impaired cell proliferation and cell viability by means of apoptosis in a time-dependent manner. They regulated the intrinsic mitochondrial cell death signaling pathway and modulated activation of caspases, Bax, iNOS, p53, NF-κB, and mitogen-activated protein kinases (p38 and JNK) through different reactive oxygen and nitrosative species.
  
  
  CONCLUSIONS
  Our data strongly support the idea that long-term hyperglycemia could act as an inducer of apoptosis in HPMCs through Amadori adducts, involving different oxidative and nitrosative reactive species.
authors.affiliation: Unidad de Investigación Hospital Universitario de Getafe, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sánchez-Rodríguez
authors.forename: Concepción
authors.initials: C
authors.lastname: Peiró
authors.forename: Susana
authors.initials: S
authors.lastname: Vallejo
authors.forename: Nuria
authors.initials: N
authors.lastname: Matesanz
authors.forename: Mariam
authors.initials: M
authors.lastname: El-Assar
authors.forename: Verónica
authors.initials: V
authors.lastname: Azcutia
authors.forename: Tania
authors.initials: T
authors.lastname: Romacho
authors.forename: Carlos Félix
authors.initials: CF
authors.lastname: Sánchez-Ferrer
authors.forename: Leocadio
authors.initials: L
authors.lastname: Rodríguez-Mañas
authors.forename: Julián
authors.initials: J
authors.lastname: Nevado
mesh_terms: D000818:Animals; D017209:Apoptosis; D002417:Cattle; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D004848:Epithelium / Q000473:pathology*; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007249:Inflammation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009584:Nitrogen / Q000378:metabolism*; D018384:Oxidative Stress; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006017:Glycolipids; C511949:N-(1,6-dideoxyfructopyranosyl)-1,3-dioleoyl-2-phosphatidylethanolamine; D010714:Phosphatidylethanolamines; D016755:Proto-Oncogene Proteins c-jun; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D009584:Nitrogen