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Amino Acid Composition, Immunoreactivity, Sequence Analysis, and Function of Bovine Hippocampal Metallothionein Isoforms

Authors

  • M. Ebadi,

    Corresponding author
    1. Department of Pharmacology, University of Nebraska College of Medicine;
      Address correspondence and reprint requests to Dr. M. Ebadi at Department of Pharmacology, University of Nebraska College of Medicine, 600 South 42nd Street, Omaha, NE 68198-6260, U.S.A.
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  • F. Perini,

    1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska; and
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  • K. Mountjoy,

    1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska; and
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  • J. S. Garvey

    1. California Institute of Technology, Pasadena, California, U.S.A.
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Address correspondence and reprint requests to Dr. M. Ebadi at Department of Pharmacology, University of Nebraska College of Medicine, 600 South 42nd Street, Omaha, NE 68198-6260, U.S.A.

Abstract

Abstract: The high concentration of zinc in the hippocampal mossy fiber axon boutons is localized in the vesicles and is mobilized by exocytosis of the zinc-laden vesicles. Because “free” zinc in excess is a neurotoxic substance inhibiting an extensive number of sulfhydryl-containing enzymes and receptor sites, we hypothesized that low-molecular-weight zinc binding proteins must exist in the hippocampus to regulate the steady-state concentration of zinc. In this communication, we report that the bovine hippocampus synthesizes metallothionein (MT) isoforms that are similar, but not identical, to those of the rat brain MT isoforms and cross-react poorly with antibodies formed against the hepatic MT isoforms, suggesting that the immunologically dominant regions of hippocampal MT (residues 1–29) are not conserved. A comparative sequence analysis of bovine hippocampal MTs and bovine hepatic MT isoforms I and II revealed a 90% sequence identity, being mostly different in residues 1–29. The results of these studies suggest that the hippocampal MT isoforms, which are synthesized on a continuous basis, may play a role in regulating the transport, accumulation, and compartmentation of zinc in the hippocampus.

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