Upregulation of calpain activity and expression in experimental allergic encephalomyelitis: a putative role for calpain in demyelination.
The degradation of myelin proteins has been implicated in destabilization of the myelin sheath in autoimmune demyelinating diseases such as multiple sclerosis (MS). In order to investigate the role of calcium-activated neutral proteinase (calpain), which degrades myelin proteins, the activity and expression (translational and transcriptional) of this enzyme were examined in spinal cords of Lewis rats with experimental allergic encephalomyelitis (EAE), an animal model of MS. In addition to calpain, the translational expression of calpastatin (endogenous inhibitor of calpain) and extent of neurofilament (NFP) and myelin protein degradation were evaluated via Western blotting in controls and rats with EAE. The transcriptional expression of millicalpain, microcalpain, and calpastatin as examined by RT-PCR was not significantly increased in EAE. However, calpain translational expression was increased by 206. 5% while the levels of 68 kDa NFP and myelin-associated glycoprotein were decreased by 42.9 and 39.7%, respectively, in animals with EAE compared to controls. Calpastatin isoforms (180, 110, 80, and 68 kDa) were significantly increased in EAE as well. The findings of increased activity and translational expression of calpain in EAE suggest a major role for this enzyme in myelinolysis associated with autoimmune demyelinating diseases.
Shields
D C
DC
Department of Neurology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.
Banik
N L
NL
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D002154:Calpain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D008970:Molecular Weight; D009186:Myelin Sheath / Q000201:enzymology*; D016900:Neurofilament Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D014176:Protein Biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D014158:Transcription, Genetic; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; D016900:Neurofilament Proteins; C033668:calpastatin; D002154:Calpain