PUTATIVE ROLE OF CALPAIN IN THE PATHOPHYSIOLOGY OF EXPERIMENTAL OPTICNEURITIS

Since myelin proteins are degraded in autoimmune demyelinating disease s such as optic neuritis, proteinases are believed to participate in m yelinolysis. Calpain (calcium activated neutral proteinase) degrades m yelin proteins at physiological pH and is found in glial and inflammat ory cells involved in demyelination, To examine the putative role of c alpain in myelinolysis, the activity and expression (translational and transcriptional) of this enzyme and endogenous inhibitor, calpastatin were examined in optic nerves of Lewis rats with experimental allergi c encephalomyelitis (EAE), an animal model of optic neuritis, Calpain activity was examined via Western blotting by measuring the extent of myelin protein degradation and calpain-specific fodrin proteolysis in optic nerves from controls versus rats with experimental optic neuriti s, RT-PCR studies demonstrated no significant change in millicalpain, microcalpain, or calpastatin expression at the mRNA level in optic ner ves from animals with experimental optic neuritis compared to controls . However, myelin associated glycoprotein (MAG) levels were decreased by 25.5 % while calpain translational expression and calpain-autolyzed fodrin levels were increased by 72.1% and 462.8% respectively, in exp erimental optic neuritis compared to controls. Translational expressio n of calpastatin isoforms (80, 68 and 55 KD) was not significantly dif ferent in rats with experimental optic neuritis compared to controls. Thus, increased activity and translational expression of calpain in ex perimental optic neuritis suggests this proteinase may participate in the degradation of myelin and cytoskeletal proteins in demyelinating d iseases such as optic neuritis. (C) 1998 Academic Press.