Microtubular proteolysis in focal cerebral ischemia
| Autor: | Mary L. Holtz, Stephen L. Minger, L. Creed Pettigrew, Nathan Hall, James W. Geddes, Susan D. Craddock |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Pathology medicine.medical_specialty Microtubule-associated protein Proteolysis Immunocytochemistry Ischemia chemistry.chemical_element Calcium Microtubules 030218 nuclear medicine & medical imaging Brain Ischemia 03 medical and health sciences 0302 clinical medicine Animal model Rats Inbred SHR medicine Animals medicine.diagnostic_test biology Calpain medicine.disease Immunohistochemistry Pathophysiology Rats Neurology chemistry biology.protein Neurology (clinical) Cardiology and Cardiovascular Medicine Microtubule-Associated Proteins 030217 neurology & neurosurgery |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 16(6) |
| ISSN: | 0271-678X |
| Popis: | Calpain, a neutral protease activated by calcium, may promote microtubular proteolysis in ischemic brain. We tested this hypothesis in an animal model of focal cerebral ischemia without reperfusion. The earliest sign of tissue injury was observed after no more than 15 min of ischemia, with coiling of apical dendrites immunolabeled to show microtubule-associated protein 2 (MAP2). After 6 h of ischemia, MAP2 immunoreactivity was markedly diminished in the infarct zone. Quantitative Western analysis demonstrated that MAP2 was almost unmeasurable after 24 h of ischemia. An increase in calpain activity, shown by an antibody recognizing calpain-cleaved spectrin fragments, paralleled the loss of MAP2 immunostaining. Double-labeled immunofluorescent studies showed that intraneuronal calpain activity preceded evidence of MAP2 proteolysis. Perikaryal immunolabeling of τ protein became increasingly prominent between 1 and 6 h in neurons located within the transition zone between ischemic and unaffected tissue. Western blot experiments confirmed that dephosphorylation of τ protein occurred during 24 h of ischemia, but was not associated with significant loss of τ antigen. We conclude that focal cerebral ischemia is associated with early microtubular proteolysis caused by calpain. |
| Databáze: | OpenAIRE |
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