The cytoprotective role of Ras in complement-mediated glomerular epithelial cell injury

In experimental membranous nephropathy, complement C5b-9-induced glomerular epithelial cell (GEC) injury leads to loss of glomerular permselectivity and proteinuria. Incubation of cultured GEC with antibody and serially-increasing concentrations of complement induced cytotoxicity in a dose-dependent...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 131(2009), 2 vom: 03. Mai, Seite 343-53
1. Verfasser: Huynh, Carl (VerfasserIn)
Weitere Verfasser: Ren, Guohui, Papillon, Joan, Guillemette, Julie, Takano, Tomoko, Cybulsky, Andrey V
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2009
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Complement Membrane Attack Complex Immunologic Factors Mitogen-Activated Protein Kinases EC 2.7.11.24 rac GTP-Binding Proteins EC 3.6.5.2 ras Proteins
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245 1 4 |a The cytoprotective role of Ras in complement-mediated glomerular epithelial cell injury 
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520 |a In experimental membranous nephropathy, complement C5b-9-induced glomerular epithelial cell (GEC) injury leads to loss of glomerular permselectivity and proteinuria. Incubation of cultured GEC with antibody and serially-increasing concentrations of complement induced cytotoxicity in a dose-dependent manner. Stable expression of constitutively-active Ras (V(12)Ras) in GEC attenuated injury significantly. In the V(12)Ras-expressing GEC, disruption of the F-actin cytoskeleton with latrunculin B or swinholide A, or stabilization of F-actin with jasplakinolide reversed the cytoprotective effect of V(12)Ras. GEC displayed cortical F-actin; V(12)Ras-expressing GEC showed smaller and more rounded morphology, and decreased activity of the Rho GTPase, Rac1, compared with control GEC. Thus, the protective effect of V(12)Ras is dependent on remodeling of the actin cytoskeleton, and may be associated with a reduction in Rac activity, thereby altering the equilibrium in the activities of Rho GTPases. Activation of Ras signaling is a novel pathway to consider in developing strategies for cytoprotection in complement-mediated injury 
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650 7 |a ras Proteins  |2 NLM 
650 7 |a EC 3.6.5.2  |2 NLM 
700 1 |a Ren, Guohui  |e verfasserin  |4 aut 
700 1 |a Papillon, Joan  |e verfasserin  |4 aut 
700 1 |a Guillemette, Julie  |e verfasserin  |4 aut 
700 1 |a Takano, Tomoko  |e verfasserin  |4 aut 
700 1 |a Cybulsky, Andrey V  |e verfasserin  |4 aut 
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