Abstract
Rat PC12 cells expressing elevated levels of transfected human Cu/Zn-superoxide dismutase (CuZn-SOD) gene were generated. These transformants (designated PC12-hSOD) closely resembled the parental cells in their morphology, growth rate, and response to nerve growth factor, but showed impaired neurotransmitter uptake. The lesion was localized to the chromaffin granule transport mechanism. We found that the pH gradient (delta pH) across the membrane, which is the main driving force for amine transport, was diminished in PC12-hSOD granules. These results show that elevation of CuZnSOD activity interferes with the transport of biogenic amines into chromaffin granules. Since neurotransmitter uptake plays an important role in many processes of the central nervous system, CuZnSOD gene-dosage may contribute to the neurobiological abnormalities of Down's syndrome.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphatases / metabolism
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Adrenal Gland Neoplasms / enzymology*
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Adrenal Gland Neoplasms / metabolism
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Adrenal Gland Neoplasms / pathology
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Animals
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Biological Transport
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Cell Membrane Permeability
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Chromaffin Granules / metabolism
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Chromaffin Granules / pathology
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Dopamine / metabolism
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Down Syndrome / enzymology
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Down Syndrome / genetics*
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Gene Expression Regulation*
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Humans
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Hydrogen-Ion Concentration
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Microscopy, Electron
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Neurotransmitter Agents / metabolism*
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Norepinephrine / metabolism
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Pheochromocytoma / enzymology*
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Pheochromocytoma / metabolism
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Pheochromocytoma / pathology
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Rats
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Superoxide Dismutase / genetics*
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Transfection
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Transformation, Genetic
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Tumor Cells, Cultured
Substances
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Neurotransmitter Agents
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Superoxide Dismutase
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Adenosine Triphosphatases
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Dopamine
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Norepinephrine