2-BFI attenuates experimental autoimmune encephalomyelitis-induced spinal cord injury with enhanced B-CK, CaATPase, but reduced calpain activity

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DOIResolve DOI: http://doi.org/10.1016/j.bbrc.2011.02.018
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TypeArticle
Journal titleBiochemical and Biophysical Research Communications
Volume406
Issue1
Pages152157; # of pages: 6
Subject2-BFI; Brain-creatine kinase; CaATPase; Calpain; Imidazoline 2 receptor; Experimentalautoimmuneencephalomyelitis; Multiple sclerosis
AbstractThe lack of disease-modifying pharmacological agents for effective treatment of multiple sclerosis (MS) still represents a large and urgent unmet medical need. Our previous studies showed that ligands to type 2 imidazoline receptors (I2R) were effective in protecting spinalcordinjury caused by experimentalautoimmuneencephalomyelitis (EAE), a mouse model of MS. In this study, we further examined the protective property of a very selective ligand of I2R, 2-(2-benzofuranyl) 2-imidazoline (2-BFI) against EAE. Importantly, a mechanism of 2-BFI-mediated protection was investigated which possibly involves an I2R binding protein, brain-creatine kinase (B-CK), as well as CaATPase and calpain. The enzymatic activity of B-CK and CaATPase was significantly reduced in EAE injured spinalcord. Reduction of B-CKactivity in EAE spinalcord may lead to energy reduction and dysfunction in cellular calcium homeostasis. Increased intracellular calcium evokes elevation of calpainactivity occurring in EAE spinalcord which causes further tissue damage. Indeed, EAE injured spinalcord showed significant reduction in CaATPase and increase calpain activities. Remarkably, spinalcord tissue from mice treated daily with 2-BFI during the progression of EAE significantly restored B-CK and CaATPase enzymatic activities and showed no induction in calpainactivity. Moreover, EAE spinalcord from 2-BFI treated mice also demonstrated better preservation of myelin; reduced axonal injury, as evidenced by the lower level of β-APP expression, and above all, highly improved neurobehavioral scores (p < 0.01; n = 10). These findings suggest that 2-BFI can be further developed as a therapeutic drug for MS treatment.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number19739564
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Record identifiere88a3720-61d2-4c09-9371-261d9c807c05
Record created2012-04-02
Record modified2016-05-09
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