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Characterisation of the hydrogen sulfide system in early diabetic kidney disease

Version 2 2024-06-03, 00:50
Version 1 2023-10-12, 03:40
journal contribution
posted on 2024-06-03, 00:50 authored by CJ Bushell, LG Forgan, Kathryn Aston-MourneyKathryn Aston-Mourney, Timothy ConnorTimothy Connor, Sean McgeeSean Mcgee, Bryony McneillBryony Mcneill
A deficiency in hydrogen sulfide has been implicated in the development and progression of diabetic chronic kidney disease. The purpose of this study was to determine the effect of diabetes on the H2S system in early-stage diabetic kidney disease. We characterised gene and protein expression profile of the enzymes that regulate H2S production and degradation, and H2S production capacity, in the kidney from 10-week-old C57BL6J db/db mice (n=6), in age-matched heterozygous controls (n=7), and in primary endothelial cells (HUVECs) exposed to high glucose. In db/db mice renal H2S levels were significantly reduced (p=0.009). Protein expression of the H2S production enzymes was differentially affected by diabetes: Cystathionine β-synthase (CBS) was significantly lower in both db/db mice and high glucose treated HUVECS (p<0.0001; p= 0.0318) whereas 3-Mercatopyruvate sulfurtransferase (3-MST) expression was higher in the db/db kidney (p<0.0001), yet lower in the HUVECs (p=0.0001). Diabetes had no effect on the expression of Cystathionine γ-lyase (CSE) in the db/db kidney (p=ns), but was associated with reduced expression in the HUVECs (p=0.0004). Protein expression of degradation enzyme Sulfide quinone reductase (SQOR) was significantly higher in db/db kidney (p=0.048) and lower in the high glucose treated HUVECs (p= 0.008). Immunofluorescence studies revealed differential localization of the H2S enzymes in the kidney, including both tubular and vascular localisation, suggestive of functionally distinct actions in the kidney. The results of this study provide foundational knowledge for future research looking at the H2S system in both kidney physiology and the aetiology of chronic diabetic kidney disease.

History

Journal

Journal of molecular endocrinology

Volume

71

Pagination

e230065-

Location

England

ISSN

0952-5041

eISSN

1479-6813

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Issue

4

Publisher

Bioscientifica