Blog
About

5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Alzheimer's amyloid-beta peptide inhibits sodium/calcium exchange measured in rat and human brain plasma membrane vesicles

      , , ,

      Neuroscience

      Elsevier BV

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Na+/Ca2+ exchange activity was measured by monitoring vesicular Ca2+ content after incubation in buffers containing 45Ca2+. When Na+-loaded vesicles were placed into Na+-free buffer, vesicular Ca2+ content increased rapidly and reached a plateau after two to three minutes. Only preaggregated amyloid-beta1-40 (Abeta1-40) and Abeta25-35 reduced vesicular Ca2+ content. Both peptides produced a maximal reduction in Ca2+ content of approximately 50%. The peptides reduced Ca2+ content with similar potency and half maximal effects were seen at less than 10 microM for Abeta25-35. Calcium-loaded vesicles mediate a rapid Ca2+/Ca2+ exchange, which also was inhibited by aggregated Abeta25-35. Aggregated Abeta25-35 did not affect the passive Ca2+ permeability of the vesicles. Aggregated Abeta25-35 reduced Ca2+ content in plasma membrane vesicles isolated from normal and Alzheimer's disease frontal cortex with less potency but the same efficacy as seen in rat brain. Aggregated Abeta25-35 did not produce nonspecific effects on vesicle morphology such as clumping or loss of intact vesicles. When placed in the buffer used to measure Ca2+ content, Congo Red at molar ratios of less than one blocked the inhibitory effect of preaggregated Abeta25-35. When added in equimolar concentrations to freshly dissolved and unaggregated Abeta25-35, Congo Red also was effective at blocking the inhibitory effect on Ca2+ content. In contrast, vitamin E (antioxidant) and N-tert-butyl-alpha-phenylnitrone (spin trapping agent) failed to block the inhibitory action of aggregated Abeta25-35. The exact mechanisms of Abeta-induced neurotoxicity in cell culture has yet to be solved. Accumulation of free radicals play a necessary role, but disruptions of Ca2+ homeostasis are also important. The data presented here are consistent with a proposed mechanism where aggregated Abeta peptides directly interact with hydrophobic surfaces of the exchanger protein and/or lipid bilayer and interfere with plasma membrane Ca2+ transport.

          Related collections

          Author and article information

          Journal
          Neuroscience
          Neuroscience
          Elsevier BV
          03064522
          July 1997
          July 1997
          : 80
          : 3
          : 675-684
          Article
          9276485
          © 1997

          Comments

          Comment on this article