title: Sialic acid attenuates puromycin aminonucleoside-induced desialylation and oxidative stress in human podocytes.
abstract: Sialoglycoproteins make a significant contribution to the negative charge of the glomerular anionic glycocalyx-crucial for efficient functioning of the glomerular permselective barrier. Defects in sialylation have serious consequences on podocyte function leading to the development of proteinuria. The aim of the current study was to investigate potential mechanisms underlying puromycin aminonucleosisde (PAN)-induced desialylation and to ascertain whether they could be corrected by administration of free sialic acid. PAN treatment of podocytes resulted in a loss of sialic acid from podocyte proteins. This was accompanied by a reduction, in the expression of sialyltransferases and a decrease in the key enzyme of sialic acid biosynthesis N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). PAN treatment also attenuated expression of the antioxidant enzyme superoxide dismutase (mSOD) and concomitantly increased the generation of superoxide anions. Sialic acid supplementation rescued podocyte protein sialylation and partially restored expression of sialyltransferases. Sialic acid also restored mSOD mRNA expression and quenched the oxidative burst. These data suggest that PAN-induced aberrant sialylation occurs as a result of modulation of enzymes involved sialic acid metabolism some of which are affected by oxidative stress. These data suggest that sialic acid therapy not only reinstates functionally important negative charge but also acts a source of antioxidant activity.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Maurice Shock Building, University Road, Leicester, LE1 9HN, UK; John Walls Renal Unit, Leicester General Hospital, Leicester, UK. Electronic address: izap1@le.ac.uk.
authors.forename: Izabella Z A
authors.initials: IZ
authors.lastname: Pawluczyk
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Maurice Shock Building, University Road, Leicester, LE1 9HN, UK.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghaderi Najafabadi
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Maurice Shock Building, University Road, Leicester, LE1 9HN, UK; John Walls Renal Unit, Leicester General Hospital, Leicester, UK.
authors.forename: Samita
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Maurice Shock Building, University Road, Leicester, LE1 9HN, UK.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Maurice Shock Building, University Road, Leicester, LE1 9HN, UK.
authors.forename: Dipti
authors.initials: D
authors.lastname: Vashi
authors.affiliation: Academic and Children's Renal Unit, University of Bristol, Southmead Hospital, Bristol, UK.
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Maurice Shock Building, University Road, Leicester, LE1 9HN, UK; John Walls Renal Unit, Leicester General Hospital, Leicester, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Topham
mesh_terms: D002478:Cells, Cultured; D004336:Drug Antagonism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D012795:Sialoglycoproteins; C001643:podocalyxin; D011692:Puromycin Aminonucleoside; D013482:Superoxide Dismutase; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid
keywords: Oxidative stress; Podocytes; Sialic acid; Sialyltransferase