gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

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AGE-induced genomic damage in kidney tubule cells: modulation by proteases, antioxidants and Candesartan

AGE-induzierter Genomschaden in Nierentubuluszellen: Modulation durch Proteasen, Antioxidantien und Candesartan

Meeting Abstract (Hypertonie 2003)

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  • presenting/speaker N. Schupp
  • A. Heidland
  • M. Scheurich
  • R. Schinzel
  • A. Klassen
  • K. Sebekova
  • H. Stopper

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV50

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch050.shtml

Published: November 11, 2004

© 2004 Schupp et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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In patients with chronic renal failure cancer incidence is enhanced. This may be related to an elevated genomic damage, which has been demonstrated by investigations of DNA repair, micronuclei formation, as well as by comet-assay analysis. Advanced glycation end products (AGEs) are markedly elevated in renal failure. We could show in the comet-assay that various AGEs (AGE-bovine serum albumin, carboxymethyllysine-BSA as well as methylglyoxal-BSA) were responsible for significant DNA damage in kidney tubule cells (LLC-PK1 cells). Comets increased by a factor of 3 to 4. The extent of this DNA damage could be modulated by various compounds:

• Pre-treatment of the cells with the proteases trypsin and bromelain abolished the AGE-induced comet formation. This supports the idea that the observed genotoxicity may be receptor-mediated and that the proteases inactivate the external domain of the cellular receptor for AGEs (RAGE). A fragment of RAGE could indeed be identified by PCR in LLC-PK1 cells.

• AGEs are reported to trigger components of oxidative stress pathways. The addition of the antioxidants 17-beta estradiol, alpha-lipoic acid and N-acetylcysteine to AGE-treated cells prevented the induction of genomic damage.

• The angiotensin II receptor antagonsist Candesartan also reduced the AGE-induced DNA damage, which probably is related to the modulation of oxidative stress. Finally, by blocking the nuclear translocation of NF-kappaB with dimethyl fumarate, we could reduce the AGE-induced genome damage, indicating an involvement of NF-kappaB in this signal pathway.