gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Protein kinase C alpha activation is involved in the induction of tubular apoptosis under diabetic condition

PKC alpha Aktivierung spielt eine Rolle bei der tubulären Apoptose bei Diabetes

Meeting Abstract (Hypertonie 2004)

  • J. Menne - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • M. Meier - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • presenting/speaker J. Park - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • M. Boehne - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • A. Goerke - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • C. Lindschau - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • M. Elger - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • F. Bahlmann - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • M. Leitges - Medizinische Hochschule Hannover, MPI (Hannover, D)
  • H. Haller - Medizinische Hochschule Hannover, MPI (Hannover, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP53

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch053.shtml

Veröffentlicht: 10. August 2005

© 2005 Menne 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

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Introduction: Tubular atrophy is a feature of diabetic nephropathy and is associated with loss of renal function. The isoforms of the PKC family are activated in response to hyperglycemia and might be involved in the occurrence of tubular apoptosis. We now analysed diabetic PKC alpha -/- animals in comparison with wild type (WT) animals.

Methods and Results: 10 weeks after induction of hyperglycemia with 2 x 125 mg streptozotocin/kg body weight the animals were sacrificed and the kidney removed and stained with Masson-Goldner trichrom stain. A significant loss of PTEC's was detected in diabetic WT animals. In diabetic PKC alpha-/- mice only few epithelial cells were damaged. This observation could also be confirmed by electron microscopy. Severe damage to the epithelium was observed in WT diabetic animals. Apoptosis of tubular epithelial cells (TUNNEL method) was widely detected in WT diabetic mice but neither in diabetic PKC alpha -/- nor in the non-diabetic mice.

We subsequently overexpressed GFP tagged-PKC alpha (PKCalpha-GFP), PKC beta (PKCbeta-GFP) and GFP alone in VSMC's. Overexpression of these molecules did not induce apoptosis. However after stimulation with TPA cells overexpressing PKCalpha-GFP became rounded with extensive blebbing as sign for apoptosis. TPA stimulation of VSMC's overexpressing PKCbeta-GFP or GFP did not lead to apotosis. Under hyperglycaemic (glucose 25 mmol/l) culture condition we observed a similar effect.

Summary: Our data suggest that activation of the PKC alpha isoform might be important in hyperglycemia mediated tubular apoptosis.