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Nephron. 2019 Jan 9:1-7. doi: 10.1159/000494390. [Epub ahead of print]

Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease.

Author information

1
CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal.
2
Centro de Química Estrutural (CQE), Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa, Portugal.
3
Portuguese Diabetes Association Education and Research Center (APDP-ERC), Lisboa, Portugal.
4
Departamento de Ciências Médicas, Universidade de Aveiro, Aveiro, Portugal.
5
Department of Nephrology, Hospital Fernando Fonseca, Lisboa, Portugal.
6
CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugalsofia.pereira@nms.unl.pt.

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

PMID:
30625494
DOI:
10.1159/000494390
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