gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Oxidized Blirubin Products (BOXes) increase levels of Endothelial Nitric Oxide Synthase Inhibitor, ADMA, in human endothelial cells

Oxidierte Bilirubin-Abbauprodukte (BOXes) erhöhen den endothelialen NO-Synthetase-Inhibitor, ADMA, in humanen Endothelzellen

Meeting Abstract

Suche in Medline nach

  • corresponding author Carla S. Jung - Neurochirurgische Klinik der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main; Surgical Neurology Branch, NINDS, NIH, Bethesda /USA
  • E. H. Oldfield - Surgical Neurology Branch, NINDS, NIH, Bethesda /USA
  • R. M. Pluta - Surgical Neurology Branch, NINDS, NIH, Bethesda /USA

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 02.15

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0298.shtml

Veröffentlicht: 23. April 2004

© 2004 Jung 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 vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Asymmetric-dimethyl-L-arginine (ADMA) produces endothelial dysfunction via endogenous inhibition of endothelial nitric oxide synthase (eNOS). Recently we have shown, that ADMA levels in the CSF were strongly correlated with arteriographic vasospasm after subarachnoid hemorrhage (SAH). We sought to determine the cellular mechanism of ADMA elevation, using the putative spasmogen oxidized bilirubin products (BOXes), and Probucol, an ADMA inhibitor.

Methods

Human umbilical vein endothelial cells (HUVECs) in EGM were used as control and HUVECs exposed to oxidized low density protein (oxLDL;10mg/dl), known to induce ADMA production, were used as positive controls. HUVECs were exposed to BOXes (1:100) for 24 hours. HUVECs exposed to oxLDL or BOXes were also co-incubated with Probucol (50μM), known to decrease ADMA levels. Cell-media and lysates were harvested to assess ADMA levels using HPLC and nitrite levels.

Results

In the media the control ADMA levels were 7± 3.6pmol/μg protein. OxLDL (positive control) (p<0.001) and BOXes (p<0.01) increased ADMA levels. Probucol decreased ADMA levels evoked by either oxLDL (p<0.001) or BOXes (p<0.01) and significantly attenuated the decrease of nitrite levels produced by BOXes and oxLDL. In cell-lysates the same effects were detected in all experimental groups.

Conclusions

BOXes increased ADMA production and release in endothelial cells. Probucol significantly decreased ADMA levels in the media and cell-lysate. These results suggest that BOXes may be responsible for endothelial dysfunction via endogenous inhibition of eNOS. ADMA-dependent endothelial dysfunction may be prevented by Probucol.