A BRIEF PERIOD OF HYPOXIA CAUSES PROTEOLYSIS OF CYTOSKELETAL PROTEINS IN HIPPOCAMPAL SLICES

Breakdown products (BDPs) resulting from the partial proteolysis of spectrin were examined in hippocampal slices after periods of hypoxia lasting for 5 or 10 min. The concentration of a approximately 155 kDa BDP increased nearly twofold after 5 min of hypoxia; further increases were not seen with 10 min episodes or 10 min of hypoxia followed by reoxygenation. The hypoxia-induced proteolysis was blocked by prior infusion of a newly introduced inhibitor of calpain (calpain inhibitor I, 200-mu-M). Together with previously published data showing improved recovery of hippocampal slices from hypoxia in the presence of calpain inhibitors, these data suggest that activation of calpain may contribute significantly to the pathophysiology of ischemia.