Inhibition of calpain-mediated apoptosis by E-64 d-reduced immediate early gene (IEG) expression and reactive astrogliosis in the lesion and penumbra following spinal cord injury in rats.

Ray, S K; Matzelle, D D; Wilford, G G; Hogan, E L; Banik, N L

Ray, S K; Matzelle, D D; Wilford, G G; Hogan, E L; Banik, N L.

Afiliación

Ray SK; Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 309, P.O. Box 250606, Charleston, SC 29425, USA.

Brain Res ; 916(1-2): 115-26, 2001 Oct 19.

Article en En | MEDLINE | ID: mdl-11597598

RESUMEN

Upregulation of calpain, a Ca(2+)-activated cysteine protease, has been implicated in apoptosis and tissue degeneration in spinal cord injury (SCI) that over time spreads from the site of injury to the surrounding regions. We examined calpain content and activity, regulation of immediate early genes (IEGs) such as c-jun and c-fos, reactive astrogliosis as the expression of glial fibrillary acidic protein (GFAP), and apoptosis-related features such as caspase-3 mRNA expression and internucleosomal DNA fragmentation in 1-cm long spinal cord segments (S1, distant rostral; S2, adjacent rostral; S3, lesion or injury; S4, adjacent caudal; and S5, distant caudal) following SCI in rats. Calpain content and production of 150 kD calpain-cleaved alpha-fodrin fragment, expression of IEGs, reactive astrogliosis, and apoptotic features were highly increased in the lesion (S3), moderately in adjacent areas (S2 and S4), and slightly in distant areas (S1 and S5) in SCI rats when compared to sham animals. Administration of the calpain-specific inhibitor E-64-d (1 mg/kg) to SCI rats continuously for 24 h inhibited calpain activity and other factors contributing to apoptosis in the lesion and surrounding areas, indicating that calpain played a key role in the pathophysiology of SCI. The results obtained from this animal model of SCI suggest that calpain inhibitor can provide neuroprotection in patients with SCI.

Asunto(s)

Apoptosis/efectos de los fármacos; Calpaína/antagonistas & inhibidores; Inhibidores de Cisteína Proteinasa/farmacología; Genes Inmediatos-Precoces/efectos de los fármacos; Leucina/análogos & derivados; Leucina/farmacología; Traumatismos de la Médula Espinal/tratamiento farmacológico; Animales; Apoptosis/fisiología; Astrocitos/efectos de los fármacos; Astrocitos/metabolismo; Astrocitos/patología; Calpaína/metabolismo; Proteínas Portadoras/efectos de los fármacos; Proteínas Portadoras/metabolismo; Caspasa 3; Caspasas/genética; Inhibidores de Cisteína Proteinasa/uso terapéutico; Fragmentación del ADN/efectos de los fármacos; Fragmentación del ADN/fisiología; Femenino; Genes Inmediatos-Precoces/fisiología; Proteína Ácida Fibrilar de la Glía/genética; Gliosis/tratamiento farmacológico; Gliosis/genética; Gliosis/fisiopatología; Leucina/uso terapéutico; Proteínas de Microfilamentos/efectos de los fármacos; Proteínas de Microfilamentos/metabolismo; Proteínas Proto-Oncogénicas c-fos/genética; Proteínas Proto-Oncogénicas c-jun/genética; ARN Mensajero/efectos de los fármacos; ARN Mensajero/metabolismo; Ratas; Ratas Sprague-Dawley; Médula Espinal/efectos de los fármacos; Médula Espinal/patología; Médula Espinal/fisiopatología; Traumatismos de la Médula Espinal/genética; Traumatismos de la Médula Espinal/fisiopatología

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Calpaína / Inhibidores de Cisteína Proteinasa / Apoptosis / Genes Inmediatos-Precoces / Leucina Tipo de estudio: Prognostic_studies Idioma: En Revista: Brain Res Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos

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