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Cyclic GMP-Dependent Pathways Protect Differentiated Oligodendrocytes from Multiple Types of Injury

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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.

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Acknowledgments

This research was supported by NIH/NINDS Grant NS13143 and Grant RG 3595A7/2 from the National Multiple Sclerosis Society (JAB).

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Authors and Affiliations

  1. Department of Neurology, Wayne State University School of Medicine, 1228 Elliman Building, 421 E. Canfield Avenue, Detroit, MI, 48201, USA

    Joyce A. Benjamins & Liljana Nedelkoska

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  1. Joyce A. Benjamins
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  2. Liljana Nedelkoska
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Correspondence to Joyce A. Benjamins.

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Special issue dedicated to Anthony Campagnoni.

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Benjamins, J.A., Nedelkoska, L. Cyclic GMP-Dependent Pathways Protect Differentiated Oligodendrocytes from Multiple Types of Injury. Neurochem Res 32, 321–329 (2007). https://doi.org/10.1007/s11064-006-9187-7

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  • DOI: https://doi.org/10.1007/s11064-006-9187-7

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