A COMPARISON OF CATHEPSIN-B PROCESSING AND DISTRIBUTION DURING NEURONAL DEATH IN RATS FOLLOWING GLOBAL-ISCHEMIA OR DECAPITATION NECROSIS

The objective of this study was to examine the possible role of the cy steine protease cathepsin B (E.C. 3.4.22.1) in the delayed neuronal de ath in rats subjected to the two-vessel occlusion model of global isch emia. Immunohistochemistry of the hippocampus showed an alteration in the distribution of cathepsin B in CA1 neurons from a lysosomal patter n to a more intense label redistributed into the cytoplasm. This chang e was not detected until the neurons had become morphologically altere d with obvious shrinkage of the cytoplasmic region. Western blotting a nd enzyme activity measurements of subcellular fractions, including ly sosomes and a cell soluble fraction, demonstrated that there was an ov erall decrease in cathepsin B activity at this time but an increase in the proenzyme form, particularly in the soluble fraction. This was fo und to be completely different from the marked loss of all forms of ca thepsin B in necrotic neurons following decapitation. (C) 1997 Elsevie r Science B.V.