Activation of calpains, calpastatin and spectrin cleavage in the brain during the pathology of fatal murine cerebral malaria.
Neuronal calpains appear to be activated uncontrollably by sustained elevation of cytosolic calcium levels under pathological conditions as well as neurodegenerative diseases. In the present study, we have characterized calpain activation in cytosolic extract of mice cerebral cortex and cerebellum using an experimental model of fatal murine cerebral malaria (FMCM). Pathology of FMCM resulted in the increase in activity of calpains in both cerebral cortex and cerebellum. Western blot analysis revealed an increase in the levels of mu-calpain (calpain-1) in the cytosolic fraction of infected cerebral cortex and cerebellum although a decrease in the level of m-calpain was observed in the cytosolic fraction of infected cerebellum and cerebral cortex. Calpain activation was further confirmed by monitoring the formation of calpain-specific spectrin breakdown products (SBDP). Protease-specific SBDP revealed the formation of calpain-generated 150kDa product in the infected cerebral cortex and cerebellum. The specific signature fragment of calpain activation and spectrin breakdown after Plasmodium berghei ANKA infection provide a strong evidence of the role of calpains during the cell death in cerebral cortex and cerebellum. Given the role of calpains in neurodegeneration and cell death, our results strongly suggest that calpains are important mediators of cell injury and neurological sequelae associated with FMCM.
Shukla
Meena
M
Division of Neurochemistry, School of Life Sciences, University of Hyderabad, Department of Animal Sciences, Hyderabad 500046, India.
Rajgopal
Yadavalli
Y
Babu
Phanithi Prakash
PP
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006868:Hydrolysis; D007150:Immunohistochemistry; D016779:Malaria, Cerebral / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D013049:Spectrin / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D013049:Spectrin; C033668:calpastatin; D002154:Calpain