Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

Research output: Contribution to journalArticle

Abstract

Background: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. Summary: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.

Original languageEnglish
Pages (from-to)17-23
JournalNephron
Volume143
Issue number1
DOIs
Publication statusPublished - 2019

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Diabetic Nephropathies
Inflammation
Environmental Monitoring
Xenobiotics
Cysteine
Oxidative Stress
Fibrosis

Keywords

  • Cysteine-S-conjugates
  • Diabetic nephropathy
  • Mercapturic acids
  • N -Acetyltransferase 8
  • Renal proximal tubular cells

Cite this

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title = "Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease",
abstract = "Background: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. Summary: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.",
keywords = "Cysteine-S-conjugates, Diabetic nephropathy, Mercapturic acids, N -Acetyltransferase 8, Renal proximal tubular cells",
author = "Clara Gon{\cc}alves-Dias and Judit Morello and Correia, {M. Jo{\~a}o} and Coelho, {Nuno R.} and Antunes, {Alexandra M.M.} and Macedo, {Maria Paula} and Monteiro, {Em{\'i}lia C.} and Karina Soto and Pereira, {Sofia A.}",
year = "2019",
doi = "10.1159/000494390",
language = "English",
volume = "143",
pages = "17--23",
journal = "Nephron. Clinical Practice",
issn = "1660-8151",
publisher = "Karger",
number = "1",

}

TY - JOUR

T1 - Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

AU - Gonçalves-Dias, Clara

AU - Morello, Judit

AU - Correia, M. João

AU - Coelho, Nuno R.

AU - Antunes, Alexandra M.M.

AU - Macedo, Maria Paula

AU - Monteiro, Emília C.

AU - Soto, Karina

AU - Pereira, Sofia A.

PY - 2019

Y1 - 2019

N2 - Background: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. Summary: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.

AB - Background: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. Summary: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.

KW - Cysteine-S-conjugates

KW - Diabetic nephropathy

KW - Mercapturic acids

KW - N -Acetyltransferase 8

KW - Renal proximal tubular cells

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