title: The Parkinsonism-associated protein DJ-1/Park7 prevents glycation damage in human keratinocyte.
abstract: Reducing sugars and dicarbonyls form covalent adducts with proteins through a nonenzymatic process known as glycation, which inactivates proteins, is increased in diabetic patients and is associated with diabetic complications, including retinopathy, cataracts, nephropathy, neuropathy, cardiomyopathy and skin defects. We recently characterized DJ-1/Park7 as a protein deglycase that repairs proteins from glycation by glyoxal and methylglyoxal, two major glycating agents which are responsible for up to 65% of glycation events. In this study, we investigated the ability of DJ-1 to prevent protein glycation in keratinocytes. Glycation of collagen and keratinocyte proteins was tested by measuring ultraviolet absorption and fluorescence emission. Protein glycation in HaCaT keratinocytes was investigated by immunodetection with anti-advanced glycation endproduct antibodies, after DJ-1 depletion or overexpression. In vitro, DJ-1 prevented glycation of collagen and keratinocyte protein extracts. In cell culture, DJ-1 depletion by small interfering RNAs resulted in a 3-fold increase in protein glycation levels. Moreover, protein glycation levels were decreased several-fold in cells overexpressing DJ-1 after addition of the Nrf2 inducer sulforaphane or after transfection with a DJ-1 plasmid. Thus, the DJ-1 deglycase plays a major role in preventing protein glycation in eukaryotic cells and might be important for preventing skin glycation.
authors.affiliation: Team Morphogénèse, Homéostasie et Pathologies, Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR 7592, Institut Jacques Monod, 15 Rue Hélène Brion, 75013, Paris, France.
authors.forename: Tamara
authors.initials: T
authors.lastname: Advedissian
authors.affiliation: Team Morphogénèse, Homéostasie et Pathologies, Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR 7592, Institut Jacques Monod, 15 Rue Hélène Brion, 75013, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Deshayes
authors.affiliation: Team Morphogénèse, Homéostasie et Pathologies, Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR 7592, Institut Jacques Monod, 15 Rue Hélène Brion, 75013, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Poirier
authors.affiliation: Team Morphogénèse, Homéostasie et Pathologies, Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR 7592, Institut Jacques Monod, 15 Rue Hélène Brion, 75013, Paris, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Viguier
authors.affiliation: Team Stress Molecules, Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR 7592 Institut Jacques Monod, 15 Rue Hélène Brion, 75013, Paris, France. Electronic address: richarme@paris7.jussieu.fr.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Richarme
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry; D002460:Cell Line; D048909:Diabetes Complications / Q000378:metabolism; D020868:Gene Silencing; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006037:Glyoxal / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017879:Isothiocyanates / Q000737:chemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D015595:Skin Aging; D013454:Sulfoxides
chemical_list: D000447:Aldehydes; D002241:Carbohydrates; D017127:Glycation End Products, Advanced; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D015513:Oncogene Proteins; D013454:Sulfoxides; D006037:Glyoxal; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C016766:sulforaphane
keywords: Carbonyl stress; Diabetes; Glycation; Maillard reaction; Protein repair; Skin