Evidence for the role of protein kinase C in astrocyte-induced proliferation of rat cerebromicrovascular endothelial cells

Neurosci Lett. 1995 Sep 15;197(3):219-22. doi: 10.1016/0304-3940(95)11941-o.

Abstract

The proliferation of cerebral endothelial cells is a crucial step in neural angiogenesis and is a process responsive to changes in the surrounding environment. Serum-free medium conditioned by rat cortical astrocytes was found to accelerate DNA synthesis, induce transient activation of protein kinase C (PKC), and increase the endogenous phosphorylation of the PKC-specific substrate, the 85 kDa MARCKS protein, in rat cerebromicrovascular endothelial cells (RCEC). The stimulatory factor(s) in astrocyte conditioned media (ACM) were heat- and trypsin-sensitive and found to have an apparent molecular weight greater than 10 kDa. 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).

MeSH terms

  • Animals
  • Astrocytes / physiology*
  • Cell Division / physiology
  • Cerebrovascular Circulation*
  • Culture Media, Serum-Free / pharmacology
  • DNA / biosynthesis
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Enzyme Activation
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Proteins*
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Phosphorylation
  • Protein Kinase C / physiology*
  • Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Culture Media, Serum-Free
  • Intracellular Signaling Peptides and Proteins
  • Marcks protein, rat
  • Membrane Proteins
  • Proteins
  • Myristoylated Alanine-Rich C Kinase Substrate
  • DNA
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate