Open AccessDiabetic nephropathy associates with deregulation of enzymes involved in kidney sulphur metabolism
Author(s) -
Uyy Elena,
Suica Viorel Iulian,
Boteanu Raluca Maria,
Safciuc Florentina,
CerveanuHogas Aurel,
Ivan Luminita,
Stavaru Crina,
Simionescu Maya,
Antohe Felicia
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15855
Subject(s) - diabetic nephropathy , kidney , kidney disease , nephropathy , diabetes mellitus , downregulation and upregulation , endocrinology , medicine , metabolism , chemistry , biology , biochemistry , gene
Abstract 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.