Ischemia induces metallothionein III expression in neurons of rat brain

Metallothionein III (MT-III) is a brain-specific member of the metallothion ein family and binds zinc in vivo. In order to confirm the precise localiza tion of MT-III in normal rat brain and the change of MT-III expression afte r transient whole brain ischemia, we raised a high affinity phagemid-antibo dy specific for rat MT-III. Immunohistochemical analysis revealed that MT-I II in normal brain is localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum. This expression pattern of MT-III was simila r to that of MT-III mRNA observed by in situ hybridization studies. ELISA a nd Northern blot analysis revealed that MT-III protein as well as mRNA leve ls were up-regulated in cerebrum soon after ischemic stress. Immunohistoche mical analysis also demonstrated intense staining in neurons in injured bra in after ischemia, which distributed in the same regions as in normal brain . These results suggest that MT-III plays an important role in protecting n eurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia.