title: Platelet-derived growth factor-BB induces cystathionine γ-lyase expression in rat mesangial cells via a redox-dependent mechanism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  PDGF-BB regulated CSE via a redox-mediated activation of Nrf2. Such action would aid the resolution of glomerular inflammatory diseases.
  
  
  BACKGROUND
  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.
authors.affiliation: Pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Mohamed I
authors.initials: MI
authors.lastname: Hassan
authors.forename: Meike
authors.initials: M
authors.lastname: Boosen
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
authors.forename: Jowita
authors.initials: J
authors.lastname: Kozlowska
authors.forename: Florian
authors.initials: F
authors.lastname: Eisel
authors.forename: Andreas
authors.initials: A
authors.lastname: von Knethen
authors.forename: Martina
authors.initials: M
authors.lastname: Beck
authors.forename: Ramadan A M
authors.initials: RA
authors.lastname: Hemeida
authors.forename: Mohamed A M
authors.initials: MA
authors.lastname: El-Moselhy
authors.forename: Farid M A
authors.initials: FM
authors.lastname: Hamada
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Beck
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000077214:Becaplermin; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism; D007518:Isoantibodies / Q000494:pharmacology; D008264:Macrophages; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology
chemical_list: D000975:Antioxidants; D007518:Isoantibodies; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C495637:Nfe2l2 protein, rat; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; C035678:anti-Thy antibody; D000077214:Becaplermin; D003542:Cystathionine gamma-Lyase