The Role of Protein Kinase C and Marcks Protein Phosphorylation in Rat Cerebromicrovascular Endothelial Cell Proliferation Induced by Astrocyte-Derived Factors

  • Danica B. Stanimirovic
  • Rita Ball
  • Josée Wong
  • Jon P. Durkin
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)

Summary

Serum-free medium conditioned by rat cortical astrocytes was found to prevent apoptosis induced by growth factor-deprivation, accelerate DNA synthesis, induce transient activation of protein kinase C (PKC), and increase the endogenous phosphorylation of the PKC-specific substrate, the 85 kD MARCKS protein, in rat cerebromicrovascular endothelial cells (RCEC). The trophic and stimulatory factor(s) in astrocyte conditioned media (ACM) were heat-and trypsin-sensitive and found to have an apparent molecular weight greater than 10 kD. The potent PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), also stimulated RCEC proliferation, whereas the inhibition of PKC by staurosporine caused a concomitant loss in ACM-induced PKC translocation, MARCKS protein phosphorylation and DNA synthesis. These findings implicate PKC activation as a critical early event in cerebral endothelial cell proliferation triggered by astrocyte-derived mitogen(s).

Keywords

Cerebral Endothelial Cell Astrocyte Conditioned Medium Basal Media Eagle Endogenous Phosphorylation MARCKS Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Résumé

Il a été trouvé qu’un milieu sans serum traité par des astrocytes du cortex de rat prévient l’apoptose induite par la privation de facteurs de croissance, accélère la synthèse d’ADN, induit une activation transitoire de la proteine kinase C (PKC), et augmente la phosphorylation endogène du substrat spécifique de la PKC, soit de la protéine MARCKS de 85 KD, chez les cellules endothéliales cérébromicrovasculaires du rat (RCEC). Le(s) facteur(s) trophique(s) et stimulant(s) du milieu traité par les astrocytes (ACM) est (sont) sensible(s) à la chaleur et à la trypsine et a (ont) un poids moléculaire apparent supérieure à 10 kD. L’activateur puissant de la PKC, le 12-O-tétradécanoyle phorbole 13-acétate (TPA) stimule la prolifération de RCEC, lorsqu’une qu’une inhibition de la PKC par la staurosporine rend l’ACM inefficace à induire la translocation de la PKC, la phosphorylation de la protéine MARCKS et la synthèse de l’ADN. Ces résultats indiquent que l’activation de la PKC est un événement critique arrivant tôt lorsque la prolifération des cellules endothéliales du cerveau est induite par un (des) mitogène(s) provenant des astrocytes.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Danica B. Stanimirovic
    • 1
  • Rita Ball
    • 1
  • Josée Wong
    • 1
  • Jon P. Durkin
    • 1
  1. 1.Cellular Neurobiology Group Institute for Biological SciencesNational Research Council of CanadaOttawaCanada

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