title: Diabetes-induced hepatic oxidative stress: a new pathogenic role for glycated albumin.
abstract: Increased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively. Our data reveal increased oxidative stress biomarkers and lipid accumulation in plasma and livers of diabetic mice, together with albumin glycoxidation. Purified mouse albumin modifications resembled those typically found in diabetic patients, i.e. degree of glycation, carbonylation, AGE levels and in terms of chemical composition. Receptor for AGE expression and reactive oxygen species production were upregulated in db/db mouse livers, together with impaired proteolytic, antioxidant and mitochondrial respiratory activities. In parallel, acute exposure of HepG2 cells to glycated albumin also elicited intracellular free radical formation. Together this study demonstrates that AGE-modified albumin can trigger damaging effects on the liver, i.e. by increasing oxidative stress, attenuating antioxidant capacity, and by impairment of hepatic proteolytic and respiratory chain enzyme activities.
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Patche
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Girard
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Catan
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boyer
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Dobi
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Planesse
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Diotel
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France; Centre Hospitalier Gabriel Martin, Saint-Paul de La Réunion, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Guerin-Dubourg
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Baret
authors.affiliation: Proteomic Unit and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: Susana B
authors.initials: SB
authors.lastname: Bravo
authors.affiliation: Proteomic Unit and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Paradela-Dobarro
authors.affiliation: Proteomic Unit and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Álvarez
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: M Faadiel
authors.initials: MF
authors.lastname: Essop
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France; CHU de La Réunion, Centre d'Investigation Clinique, Saint-Denis F-97400, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France. Electronic address: emmanuel.bourdon@univ-reunion.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourdon
authors.affiliation: Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France. Electronic address: rophil@univ-reunion.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rondeau
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D000093423:Glycated Serum Albumin
chemical_list: D000951:Antigens, Neoplasm; D005609:Free Radicals; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D012709:Serum Albumin; C498978:MOK protein, human; D020928:Mitogen-Activated Protein Kinases; D000093423:Glycated Serum Albumin
keywords: AGE; Advanced glycation endproducts; Diabetes; HepG2; Liver; Mitochondria; Oxidative stress; RAGE