Sialic acid attenuates puromycin aminonucleoside-induced desialylation and oxidative stress in human podocytes

Izabella Z A Pawluczyk, Maryam Ghaderi Najafabadi, Samita Patel, Priyanka Desai, Dipti Vashi, Moin A Saleem, Peter S Topham

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)258-68
Number of pages11
JournalExperimental Cell Research
Volume320
Issue number2
DOIs
Publication statusPublished - 15 Jan 2014

Keywords

  • Cells, Cultured
  • Drug Antagonism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • N-Acetylneuraminic Acid
  • Oxidative Stress
  • Podocytes
  • Protein Processing, Post-Translational
  • Puromycin Aminonucleoside
  • Sialoglycoproteins
  • Sialyltransferases
  • Superoxide Dismutase

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