Diabetic nephropathy associates with deregulation of enzymes involved in kidney sulphur metabolism.

Autor: Uyy E; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Suica VI; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Boteanu RM; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Safciuc F; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Cerveanu-Hogas A; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Ivan L; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Stavaru C; 'Cantacuzino' National Institute of Research and Development for Microbiology and Immunology, Bucharest, Romania., Simionescu M; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania., Antohe F; Institute of Cellular Biology and Pathology 'Nicolae Simionescu', Bucharest, Romania.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2020 Oct; Vol. 24 (20), pp. 12131-12140. Date of Electronic Publication: 2020 Sep 16.
DOI: 10.1111/jcmm.15855
Abstrakt: Nephropathy is a major chronic complication of diabetes. A crucial role in renal pathophysiology is played by hydrogen sulphide (H 2 S) that is produced excessively by the kidney; however, the data regarding H 2 S bioavailability are inconsistent. We hypothesize that early type 1 diabetes (T1D) increases H 2 S production by a mechanism involving hyperglycaemia-induced alterations in sulphur metabolism. Plasma and kidney tissue collected from T1D double transgenic mice were subjected to mass spectrometry-based proteomic analysis, and the results were validated by immunological and gene expression assays.T1D mice exhibited a high concentration of H 2 S in the plasma and kidney tissue and histological, showed signs of subtle kidney fibrosis, characteristic for early renal disease. The shotgun proteomic analyses disclosed that the level of enzymes implicated in sulphate activation modulators, H 2 S-oxidation and H 2 S-production were significantly affected (ie 6 up-regulated and 4 down-regulated). Gene expression results corroborated well with the proteomic data. Dysregulation of H 2 S enzymes underly the changes occurring in H 2 S production, which in turn could play a key role in the initiation of renal disease. The new findings lead to a novel target in the therapy of diabetic nephropathy. Mass spectrometry data are available via ProteomeXchange with identifier PXD018053.
(© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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