Cyclic GMP-dependent pathways protect differentiated oligodendrocytes from multiple types of injury.

Abstract:

:The cyclic GMP analog 8-bromo-cyclic GMP (8-Br-cGMP) protects differentiated murine oligodendrocytes (OLs) from caspase-mediated death initiated by staurosporine, thapsigargin or kainate. Caspase-independent death caused by high levels of NO is also partially prevented by 8-Br-cGMP. Inhibitors of protein kinase G (cGMP-dependent protein kinase, cGK) reversed protection, supporting involvement of cGK. Since NO stimulates soluble guanylate cyclase, increasing cGMP, we treated OLs with low levels of NO and observed partial protection against thapsigargin, staurosporine and kainate. Two inhibitors of mitochondrial pore transition (MPT), cyclosporin A and bongkrekic acid, were poorly protective, indicating that cGMP is not acting primarily by blocking MPT. 8Br-cGMP was more effective than 8Br-cAMP in protecting against staurosporine or release of intracellular Ca(++) by thapsigargin. The cAMP analog exhibited little or no protection against kainate or high levels of NO. Thus cGK signaling is more effective than protein kinase A or phosphodiesterase 3 signaling in preventing OL death.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Benjamins JA,Nedelkoska L

doi

10.1007/s11064-006-9187-7

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

321-9

issue

2

eissn

0364-3190

issn

1573-6903

journal_volume

32

pub_type

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