4 research outputs found
Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury
Hydrogen sulfide (H2S) is known to act protectively during renal
ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in
acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of
cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient
(Cth−/−) mice whose renal H2S levels were approximately 50% of control (wild-
type) mice. Although levels of serum creatinine and renal expression of AKI
marker proteins were equivalent between Cth−/− and control mice, histological
analysis revealed that IRI caused less renal tubular damage in Cth−/− mice.
Flow cytometric analysis revealed that renal population of infiltrated
granulocytes/macrophages was equivalent in these mice. However, renal
expression levels of certain inflammatory cytokines/adhesion molecules
believed to play a role in IRI were found to be lower after IRI only in Cth−/−
mice. Our results indicate that the systemic CTH loss does not deteriorate but
rather ameliorates the immediate AKI outcome probably due to reduced
inflammatory responses in the kidney. The renal expression of CTH and other
H2S-producing enzymes was markedly suppressed after IRI, which could be an
integrated adaptive response for renal cell protection
Supplementary material for the article: Wedmann, R.; Onderka, C.; Wei, S.; Szijártó, I. A.; Miljkovic, J. L.; Mitrovic, A.; Lange, M.; Savitsky, S.; Yadav, P. K.; Torregrossa, R.; et al. Improved Tag-Switch Method Reveals That Thioredoxin Acts as Depersulfidase and Controls the Intracellular Levels of Protein Persulfidation. Chemical Science 2016, 7 (5), 3414–3426. https://doi.org/10.1039/c5sc04818d
Supplementary material for: [https://doi.org/10.1039/c5sc04818d]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1925
Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation
Hydrogen sulfide (H2S) has emerged as a signalling molecule capable of regulating several important physiological functions such as blood pressure, neurotransmission and inflammation. The mechanisms behind these effects are still largely elusive and oxidative posttranslational modification of cysteine residues (protein persulfidation or S-sulfhydration) has been proposed as the main pathway for H2S-induced biological and pharmacological effects. As a signalling mechanism, persulfidation has to be controlled. Using an improved tag-switch assay for persulfide detection we show here that protein persulfide levels are controlled by the thioredoxin system. Recombinant thioredoxin showed an almost 10-fold higher reactivity towards cysteine persulfide than towards cystine and readily cleaved protein persulfides as well. This reaction resulted in H2S release suggesting that thioredoxin could be an important regulator of H2S levels from persulfide pools. Inhibition of the thioredoxin system caused an increase in intracellular persulfides, highlighting thioredoxin as a major protein depersulfidase that controls H2S signalling. Finally, using plasma from HIV-1 patients that have higher circulatory levels of thioredoxin, we could prove depersulfidase role in vivo.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3543