Platelet-derived growth factor-BB induces cystathionine γ-lyase expression in rat mesangial cells via a redox-dependent mechanism
| Autor: | Mohamed I, Hassan, Meike, Boosen, Liliana, Schaefer, Jowita, Kozlowska, Florian, Eisel, Andreas, von Knethen, Martina, Beck, Ramadan A M, Hemeida, Mohamed A M, El-Moselhy, Farid M A, Hamada, Karl-Friedrich, Beck, Josef, Pfeilschifter |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Mice
Knockout Research Papers with Commentaries NF-E2-Related Factor 2 Macrophages Becaplermin Cystathionine gamma-Lyase Proto-Oncogene Proteins c-sis Antioxidants Gene Expression Regulation Enzymologic Rats Rats Sprague-Dawley Mice Glomerulonephritis Isoantibodies parasitic diseases Mesangial Cells Animals Reactive Oxygen Species Oxidation-Reduction Cells Cultured Spleen |
| Zdroj: | British journal of pharmacology. 166(8) |
| ISSN: | 1476-5381 |
| Popis: | So far, there is only limited information about the regulation of the endogenous synthesis of hydrogen sulfide (H(2) S), an important gaseous signalling molecule. This study was done to evaluate the redox-dependent signalling events that regulate the expression of the H(2) S synthesising enzyme cystathionine-γ-lyase (CSE) in rat mesangial cells.The effects of platelet-derived growth factor (PDGF)-BB and antioxidants on CSE expression and activity in cultured rat renal mesangial cells were assessed. Activity of nuclear factor erythroid-2-related factor-2 (Nrf2) was measured as the binding capacity to a radiolabelled consensus element by electrophoretic mobility shift assay (EMSA). Furthermore, CSE and Nrf2 expression was analysed in a rat model of anti-Thy-1-induced glomerulonephritis by immunohistochemistry.Treatment of mesangial cells with PDGF-BB resulted in a marked time- and dose-dependent up-regulation of CSE mRNA and protein levels, as well as CSE activity accompanied with increased formation of reactive oxygen species. Remarkably, co-administration of antioxidants, such as N-acetylcysteine, ebselen or diphenylene iodonium chloride, drastically reduced PDGF-BB-induced CSE expression. PDGF-BB induced binding of Nrf2 to a corresponding consensus antioxidant element in a redox-dependent manner. Furthermore, PDGF-BB-induced CSE expression in mouse mesangial cells was completely abolished in Nrf2 knockout mice compared with wild-type mice. In a rat model of anti-Thy-1-induced proliferative glomerulonephritis, we observed a marked up-regulation of CSE protein paralleled by a stabilization of Nrf2 protein.PDGF-BB regulated CSE via a redox-mediated activation of Nrf2. Such action would aid the resolution of glomerular inflammatory diseases.This article is commented on by Gallyas, pp. 2228-2230 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.01976.x. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|