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Cyclic GMP is more effective than cyclic AMP or GDNF in protecting mature oligodendrocytes from cell death
Author(s) -
Benjamins J. A.,
Nedelkoska L.
Publication year - 2002
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 - 10.1046/j.1471-4159.81.s1.19_2.x
Subject(s) - staurosporine , glial cell line derived neurotrophic factor , microbiology and biotechnology , thapsigargin , programmed cell death , calphostin , protein kinase a , forskolin , kainate receptor , biology , chemistry , pharmacology , kinase , receptor , apoptosis , biochemistry , glutamate receptor , endoplasmic reticulum , neurotrophic factors , ampa receptor
During immune‐mediated or ischemic attack, oligodendrocytes (OLs) receive a barrage of signals, both protective and injurious. The specific ligands at the site of damage in vivo vary widely in type and concentration. Using cultured mature mouse OLs, we have focused on four models of cell death which represent common pathways initiated by a number of ligands. These include (1) staurosporine, which induces peroxynitrite formation and subsequent release of cytochrome c; (2) thapsigargin, which disrupts Ca++ homeostasis in the endoplasmic reticulum; (3) kainate, which activates non‐NMDA receptors; and (4) SNAP and NOC‐18, which release NO. GDNF protects only against cell death induced by staurosporine, and acts via PI‐3‐kinase but not MAP kinase to protect. Elevation of cyclic AMP by addition of 8Br‐cyclic AMP or forskolin protects against staurosporine, but does not increase the protective effect of GDNF when added in combination. In addition, elevation of cyclic AMP protects against cell death initiated by thapsigargin, but not kainate or SNAP. Inhibition of protein kinase C with calphostin protects only against kainate. Of the possible protective agents tested, 8Br‐cyclic GMP is the only one which protects OLs in all four models of cell death. These results highlight the importance of signaling via cyclic GMP in survival pathways in mature OLs. Acknowledgements: Supported by grant NS13143 from NIH and grant RG 3030A/6 from the National Multiple Sclerosis Society.