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    Decreases in Plasma Membrane Ca2+-ATPase in Brain Synaptic Membrane Rafts from Aged Rats

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    Issue Date
    2012-12
    Author
    Jiang, Lei
    Bechtel, Misty D.
    Galeva, Nadezhda A.
    Williams, Todd D.
    Michaelis, Elias K.
    Michaelis, Mary Lou
    Publisher
    Wiley
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    This is the peer reviewed version of the following article: Jiang, L., Bechtel, M. D., Galeva, N. A., Williams, T. D., Michaelis, E. K., & Michaelis, M. L. (2012). Decreases in Plasma Membrane Ca2+-ATPase in Brain Synaptic Membrane Rafts from Aged Rats. Journal of Neurochemistry, 123(5), 689–699. http://doi.org/10.1111/j.1471-4159.2012.07918.x, which has been published in final form at http://doi.org/10.1111/j.1471-4159.2012.07918.x This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
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    Abstract
    Precise regulation of free intracellular Ca2+ concentrations [Ca2+]i is critical for normal neuronal function, and alterations in Ca2+ homeostasis are associated with brain aging and neurodegenerative diseases. One of the most important proteins controlling [Ca2+]i is the plasma membrane Ca2+-ATPase (PMCA), the high affinity transporter that fine tunes the cytosolic nanomolar levels of Ca2+. We previously found that PMCA protein in synaptic plasma membranes (SPMs) is decreased with advancing age and the decrease in enzyme activity is much greater than that in protein levels. In the present study, we isolated raft and non-raft fractions from rat brain SPMs and used quantitative mass spectrometry to show that the specialized lipid microdomains in SPMs, the rafts, contain 60% of total PMCA, comprised of all four isoforms. The raft PMCA pool had the highest specific activity and this decreased progressively with age. The reduction in PMCA protein could not account for the dramatic activity loss. Addition of excess CaM to the assay did not restore PMCA activity to that in young brains. Analysis of the major raft lipids revealed a slight age-related increase in cholesterol levels and such increases might enhance membrane lipid order and prevent further loss of PMCA activity.
    URI
    http://hdl.handle.net/1808/24220
    DOI
    https://doi.org/10.1111/j.1471-4159.2012.07918.x
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    • Pharmacy Scholarly Works [280]
    Citation
    Jiang, L., Bechtel, M. D., Galeva, N. A., Williams, T. D., Michaelis, E. K., & Michaelis, M. L. (2012). Decreases in Plasma Membrane Ca2+-ATPase in Brain Synaptic Membrane Rafts from Aged Rats. Journal of Neurochemistry, 123(5), 689–699. http://doi.org/10.1111/j.1471-4159.2012.07918.x

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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