Abstract

Our general goal was to non-invasively evaluate kidney tubular dysfunction. We developed a strategy based on cysteine (Cys) disulfide stress mechanism that underlies kidney dysfunction. There is scarce information regarding the fate of Cys-disulfides (CysSSX), but evidence shows they might be detoxified in proximal tubular cells by the action of N-acetyltransferase 8 (NAT8). This enzyme promotes the addition of an N-acetyl moiety to cysteine-S-conjugates, forming mercapturates that are eliminated in urine. Therefore, we developed a strategy to quantify mercapturates of CysSSX in urine as surrogate of disulfide stress and NAT8 activity in kidney tubular cells. We use a reduction agent for the selective reduction of disulfide bonds. The obtained N-acetylcysteine moiety of the mercapturates from cysteine disulfides was monitored by fluorescence detection. The method was applied to urine from mice and rat as well as individuals with healthy kidney and kidney disease.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages109-120
Number of pages12
DOIs
Publication statusPublished - 2021

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1306
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Cysteine
  • Disulfide stress
  • Kidney function marker
  • Mercapturate pathway
  • Mercapturic acid
  • N-acetyltransferase-8
  • Proximal tubular cell
  • Uremic toxins

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