gms | German Medical Science

125. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

22. - 25.04.2008, Berlin

The viral FLIP molecule K13 of human herpesvirus-8 induces manganese superoxide dismutase in endothelial cells and protects against superoxide-induced cell death

Meeting Abstract

  • corresponding author M. Thurau - Department of Surgery, Division of Molecular and Experimental Surgery, University Clinical Center, Erlangen
  • G. Sander - Department of Surgery, Division of Molecular and Experimental Surgery, University Clinical Center, Erlangen
  • N. Gonin-Laurent - Department of Surgery, Division of Molecular and Experimental Surgery, University Clinical Center, Erlangen
  • K. Weinländer - Department of Surgery, Division of Molecular and Experimental Surgery, University Clinical Center, Erlangen
  • K. R. Alkharsah - Medical School Hannover, Department of Virology, Hannover
  • F. Neipel - Institute for Clinical and Molecular Virology, University Hospital Erlangen, Erlangen
  • T. F. Schulz - Medical School Hannover, Department of Virology, Hannover
  • W. Hohenberger - Institute for Clinical and Molecular Virology, University Hospital Erlangen, Erlangen
  • M. Stürzl - Department of Surgery, Division of Molecular and Experimental Surgery, University Clinical Center, Erlangen

Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. Doc08dgch9071

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgch2008/08dgch341.shtml

Veröffentlicht: 16. April 2008

© 2008 Thurau et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Kaposi’s sarcoma (KS) is an endothelial tumor and human herpesvirus-8 (HHV-8) is the causative agent of this disease. HHV-8 encoded viral FLICE-inhibitory protein K13 is regarded as an important factor for the pathogenesis of KS. K13 is an inhibitor of cell death both by blocking receptor-induced death signaling and by up-regulation of cellular anti-apoptotic proteins. Both activities may protect infected cells from death induced by cytotoxic T-cells which infiltrate into KS lesions. However, it is not known how HHV-8-infected cells circumvent cell damage caused by oxidative stress in the inflammatory milieu of KS lesions.

Materials and methods: 2-D difference gel electrophoresis was performed with Cy3-labeled human endothelial cells stably expressing K13 and Cy5-labeled control cells. Fluorescence was quantified with a FLA-5000 laser scanner (Fuji).Cell Death and superoxide production was measured by flow cytometry with AnnexinV/propidium iodide and dihydroethidium labeling.Immunhistochemistry and confocal laser scanning microscopy was performed with a polyclonal MnSOD-specific antibody.

Results: With comparative proteome analysis we identified the mitochondrial anti-oxidant manganese superoxide dismutase (MnSOD) as a strongly induced protein by K13 in primary endothelial cells. MnSOD is a primary defense enzyme against oxidative stress. Congruously, superoxide production was inhibited in K13-expressing cells and these cells were protected against superoxide-induced death. In addition, the up-regulation of MnSOD was confirmed in HHV-8-infected HUVEC.

Conclusion: These findings link K13 to the inhibition of mitochondrial superoxide accumulation and reveal a novel strategy of cell death prevention by K13. The reduction of oxidative-induced cell damage in the aggressive milieu of KS lesions may be an important process in the pathogenesis of KS.