AMINO-ACID-COMPOSITION, IMMUNOREACTIVITY, SEQUENCE-ANALYSIS, AND FUNCTION OF BOVINE HIPPOCAMPAL METALLOTHIONEIN ISOFORMS

The high concentration of zinc in the hippocampal messy fiber axon bou tons is localized in the vesicles and is mobilized by exocytosis of th e zinc-laden vesicles. Because ''free'' zinc in excess is a neurotoxic substance inhibiting an extensive number of sulfhydryl-containing enz ymes and receptor sites, we hypothesized that low-molecular-weight zin c binding proteins must exist in the hippocampus to regulate the stead y-state concentration of zinc, In this communication, we report that t he bovine hippocampus synthesizes metallothionein (MT) isoforms that a re similar, but not identical, to those of the rat brain MT isoforms a nd cross-react poorly with antibodies formed against the hepatic MT is oforms, suggesting that the immunologically dominant regions of hippoc ampal MT (residues 1-29) are not conserved. A comparative sequence ana lysis of bovine hippocampal MTs and bovine hepatic MT isoforms I and I I revealed a 90% sequence identity, being mostly different in residues 1-29. The results of these studies suggest that the hippocampal MT is oforms, which are synthesized on a continuous basis, may play a role i n regulating the transport, accumulation, and compartmentation of zinc in the hippocampus.