Ca2+-mediated degradation of central nervous system (CNS) proteins: topographic and species variation.

Incubation of homogenates of rat, rabbit, and bovine spinal cord and of bovine brain white and gray matter in the presence of calcium (5 mM) produced an extensive degradation of the neurofilament triplet proteins (NFP; 200 K, 150 K, and 69 K). The breakdown products of the NFPs were identified by immunoblot. The glial fibrillary acidic protein (GFAP), microtubular proteins (MTP), and myelin proteins were also degraded. The 150 K NFP was more susceptible than the other NFPs. The extent of calcium-mediated degradation was slightly greater with rat spinal cord than the others. Bovine brain white matter had more activity than gray, which had no appreciable degradative activity. The breakdown was prevented by both EGTA and leupeptin but a similar concentration of MgCl2 (5 mM) had no effect. These results suggest that NFPs are degraded by a Ca2+-activated neutral proteinase in the central nervous system (CNS) of several species. The lesser activity in gray matter suggests that the enzyme is enriched in axons, myelin, and/or oligodendroglial cells.