The cyclic GMP-protein kinase G pathway regulates cytoskeleton dynamics and motility in astrocytes

J Neurochem. 2007 Jul;102(1):216-30. doi: 10.1111/j.1471-4159.2007.04464.x.

Abstract

We have previously demonstrated that inflammatory compounds that increase nitric oxide (NO) synthase expression have a biphasic effect on the level of the NO messenger cGMP in astrocytes. In this work, we demonstrate that NO-dependent cGMP formation is involved in the morphological change induced by lipopolysaccharide (LPS) in cultured rat cerebellar astroglia. In agreement with this, dibutyryl-cGMP, a permeable cGMP analogue, and atrial natriuretic peptide, a ligand for particulate guanylyl cyclase, are both able to induce process elongation and branching in astrocytes resulting from a rapid, reversible and concentration-dependent redistribution of glial fibrillary acidic protein (GFAP) and actin filaments without significant change in protein levels. These effects are also observed in astrocytes co-cultured with neurons. The cytoskeleton rearrangement induced by cGMP is prevented by the specific protein kinase G inhibitor Rp-8Br-PET-cGMPS and involves downstream inhibition of RhoA GTPase since is not observed in cells transfected with constitutively active RhoA. Furthermore, dibutyryl-cGMP prevents RhoA-membrane association, a step necessary for its interaction with effectors. Stimulation of the cGMP-protein kinase G pathway also leads to increased astrocyte migration in an in vitro scratch-wound assay resulting in accelerated wound closure, as seen in reactive gliosis following brain injury. These results indicate that cGMP-mediated pathways may regulate physio-pathologically relevant responses in astroglial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Antimetabolites
  • Astrocytes / metabolism*
  • Atrial Natriuretic Factor / metabolism
  • Blotting, Western
  • Bromodeoxyuridine
  • Bucladesine / metabolism
  • Cell Movement / physiology
  • Cells, Cultured
  • Cyclic GMP-Dependent Protein Kinases / physiology*
  • Cytoskeleton / metabolism*
  • Fluorescent Dyes
  • Glial Fibrillary Acidic Protein / metabolism
  • Indoles
  • Inflammation / pathology
  • Lipopolysaccharides / pharmacology
  • Neuroglia / physiology
  • Nitric Oxide / metabolism
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology
  • Transfection
  • Wounds and Injuries / pathology
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Actins
  • Antimetabolites
  • Fluorescent Dyes
  • Glial Fibrillary Acidic Protein
  • Indoles
  • Lipopolysaccharides
  • Nitric Oxide
  • DAPI
  • Bucladesine
  • Atrial Natriuretic Factor
  • Cyclic GMP-Dependent Protein Kinases
  • rhoA GTP-Binding Protein
  • Bromodeoxyuridine