Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils

Cytochrome c was detected by immunoblotting in the cytosolic fraction 3 h a fter 5-min ischemia in the non-ischemia-tolerant CA1 region in which about 96% of neurons had developed delayed neuronal death, while less cytosolic c ytochrome c was detected in the ischemia-tolerance-induced CA1 region where many more neurons survived. In the immunohistochemical study using anti-no n-native cytochrome c monoclonal antibody, immunoreactivity was observed th roughout the cytoplasm in the non-ischemia-tolerant CA1 neurons, but not in the normal and ischemia-tolerant CA1 neurons. Then we determined whether B cl-2, Bar, Bcl-x(L) and Bcl-x(S), which regulate the release of cytochrome c from mitochondria, were altered in the ischemia-tolerant CA1 region. Bcl- 2 and Bar were up-regulated in the ischemia-tolerant group, but Bcl-x(L) an d Bcl-x(S) showed no apparent difference in their expression. These results suggest that cytochrome c release is prevented in CA1 neurons in gerbils i n which ischemia-tolerance had been induced and that the altered ratio of B cl-2 to Bar may play a part in this mechanism. (C) 2000 Elsevier Science Ir eland Ltd. All rights reserved.