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The cyclic GMP‐protein kinase G pathway regulates cytoskeleton dynamics and motility in astrocytes
Author(s) -
Borán Mariela Susana,
García Agustina
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04464.x
Subject(s) - rhoa , microbiology and biotechnology , protein kinase a , cgmp dependent protein kinase , soluble guanylyl cyclase , astrocyte , chemistry , actin cytoskeleton , cytoskeleton , biology , nitric oxide , signal transduction , kinase , biochemistry , mitogen activated protein kinase kinase , cell , endocrinology , guanylate cyclase , central nervous system
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.