title: Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia.
abstract: To assess the effects of Aleglitazar on hyperglycaemia-induced apoptosis.
  
  
  
  We incubated human cardiomyocytes, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout or wild-type mice in normoglycaemic or hyperglycaemic conditions (glucose 25 mM). Cells were treated with different concentrations of Aleglitazar for 48 h. We measured viability, apoptosis, caspase-3 activity, cytochrome-C release, total antioxidant capacity and reactive oxygen species formation in the treated cardiomyocytes. Human cardiomyocytes were transfected with short interfering RNA against peroxisome proliferator-activated receptor-α or peroxisome proliferator-activated receptor-γ.
  
  
  
  Aleglitazar attenuated hyperglycaemia-induced apoptosis, caspase-3 activity and cytochrome-C release and increased viability in human cardiomyocyte, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout and wild-type mice. Hyperglycaemia reduced the antioxidant capacity and Aleglitazar significantly blunted this effect. Hyperglycaemia-induced reactive oxygen species production was attenuated by Aleglitazar in both human cardiomyocyte and wild-type mice cardiomyocytes. Aleglitazar improved cell viability in cells exposed to hyperglycaemia. The protective effect was partially blocked by short interfering RNA against peroxisome proliferator-activated receptor-α alone and short interfering RNA against peroxisome proliferator-activated receptor-γ alone and completely blocked by short interfering RNA to both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ.
  
  
  
  Aleglitazar protects cardiomyocytes against hyperglycaemia-induced apoptosis by combined activation of both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in a short-term vitro model.
authors.affiliation: 1 Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 2 Department of Anesthesiology, Kunming Tongren Hospital, Kunming, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Chen
authors.affiliation: 3 Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Yochai
authors.initials: Y
authors.lastname: Birnbaum
authors.affiliation: 4 Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
authors.forename: Manjyot K
authors.initials: MK
authors.lastname: Nanhwan
authors.affiliation: 5 Section of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Mandeep
authors.initials: M
authors.lastname: Bajaj
authors.affiliation: 4 Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Ye
authors.affiliation: 1 Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Jinqiao
authors.initials: J
authors.lastname: Qian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006943:Hyperglycemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010080:Oxazoles / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
chemical_list: D007004:Hypoglycemic Agents; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D013876:Thiophenes; C542437:aleglitazar; D045304:Cytochromes c; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Aleglitazar; apoptosis; cardiomyocytes; hyperglycaemia; peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ agonist