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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
