Calcium-mediated breakdown of glial filaments and neurofilaments in rat optic nerve and spinal cord
- 23 Downloads
Disruptive effects of calcium upon neurofilaments and glial filaments were studied in white matter of rat optic nerve and spinal cord and in rat peripheral nerve. Filament ultrastructure and tissue protein composition were compared following a calcium influx into excised tissues. A calcium influx was induced by freeze-thawing tissues in media containing calcium (5 mM) while control tissues were freeze-thawed in the presence of EGTA (5 mM). Experimental and control tissues were either fixed by immersion in glutaraldehyde and processed for electron microscopic examination or homogenized in a solubilizing buffer and analyzed for protein content by SDS-polyacrylamide gel electrophoresis. Morphological studies showed that calcium influxes led to the loss of neurofilaments and glial filaments and to their replacement by an amorphous granular material. These morphological changes were accompanied by the loss of neurofilament triplet proteins and glial fibrillary acidic (GFA) protein from whole-tissue homogenates. In addition, a calcium-sensitive 58,000-mol-wt protein was identified in rat optic and peripheral nerve. The findings indicate the widespread occurrence of neurofilament proteolysis following calcium influxes into CNS and PNS tissues. The parallel breakdown of glial filaments and loss of GFA protein subunits suggest the presence of additional calcium-activated proteases(s) in astroglial cells.
KeywordsSpinal Cord Peripheral Nerve Glial Fibrillary Acidic Protein Granular Material Calcium Influx
Unable to display preview. Download preview PDF.
- 1.Anderton, B. H., Ayers, M., andThorpe, R. 1978. Neurofilaments from mammalian central and peripheral nerve share certain polypeptides. FEBS Lett. 103:148–151.Google Scholar
- 5.Fields, K. L., andYen, S. H. 1979. Antibodies to neurofilament, glial filament and fibroblast intermediate filament proteins bind to different cell types of the nervous system. Page 131, inCondeelis, J., Satir, P., andBurridge, K. (eds.), The Cytoskeleton: Membranes and Movements, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
- 9.Lasek, R. J., andBlack, M. M. 1977. How do axons, stop growing? Some clues from the metabolism of the proteins in the slow component of axonal transport. Pages 161–169,in Roberts, S., Lajtha, A., andGispen, W. H. (eds.), Mechanisms, Regulation and Special Functions of Protein Synthesis in the Brain, Elsevier-North Holland Biomedical Press, Amsterdam.Google Scholar
- 10.Lasek, R. J., andHoffman, P. N. 1976. The neuronal cytoskeleton, axonal transport and axonal growth. Pages 1021–1049,in Goldman, R., Pollard, T., andRosenbaum, J. (eds.), Cell Motility, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
- 12.Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of bacteriophage T4. Nature 277:680–685.Google Scholar
- 21.Schachner, M., Hedley-Whyte, E. T., Hsu, D. W., Schoonmaker, G., andBignami, A.. Ultrastructural localization of glial fibrillary protein in mouse cerebellum by immunoperoxidase labeling. J. Cell Biol. 75:67–73.Google Scholar
- 24.Schlaepfer, W. W. 1974. Structural alterations of peripheral nerve induced by the calcium ionophore, A23187. Brain Res. 136:1–9.Google Scholar
- 33.Schlaepfer, W. W., andZimmerman, U. J. P. 1980. Calcium-dependent breakdown of glial filaments in rat optic nerve and spinal cord. J. Neuropathol. Exp. Neurol. 39:388.Google Scholar
- 34.Schook, W. J., andNorton, W. T. 1975. On the composition of axonal neurofilaments. Trans. Am. Soc. Neurochem. 1:214.Google Scholar