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

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.

• Authors: Mariela Susana Borán, Agustina García
• Journal: Journal of neurochemistry (J Neurochem) Vol. 102 Issue 1 Pg. 216-30 (Jul 2007) ISSN: 0022-3042 [Print] England
• PMID: 17564679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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)