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Mitochondrial ROS Production Initiates Aβ1-40-Mediated Up-Regulation of L-Type Ca2+ Channels during Chronic Hypoxia

  • IAN M. FEARON
  • STEPHEN T. BROWN
  • KRISTIN HUDASEK
  • JASON L. SCRAGG
  • JOHN P. BOYLE
  • CHRIS PEERS
Conference paper
Part of the ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY book series (AEMB, volume 580)

Abstract

Exposure to chronic hypoxia (CH) initiates cellular responses designed to counteract this deleterious stimulus, providing a physiological response to low oxygen. However, long-term exposure to CH, such as that which occurs in cardiorespiratory diseases such as ischaemic stroke, can also have pathological consequences. In many cases, CH alters the transcription of genes encoding numerous proteins, secondary to accumulation of the transcriptional activator hypoxia inducible factor-1 (HIF-1) (Schofield and Ratcliffe, 2004). In contrast, we recently reported that hypoxic regulation of the plasma membrane expression of L-type Ca2+ channel α1c subunits occurred in a post-transcriptional manner due to the trafficking of these subunits towards, and / or their retention within, the plasma membrane (Scragg et al., 2004). This process involved the altered production of amyloid β peptides (A Ps), since it was inhibited by selective inhibitors of the secretases involved in the production of these peptides, and mimicked by exogenous AβP. This regulation of the functional membrane expression of a voltage-gated Ca2+ channel may contribute to the Ca2+ dyshomeostasis seen in Alzheimer’s disease, a prevalent disorder in which hypoxia / ischaemia is a predisposing factor (Moroney et al., 1996).

Keywords

Reactive Oxygen Species Production HEK293 Cell Electron Transport Chain Chronic Hypoxia Hypoxic Regulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2006

Authors and Affiliations

  • IAN M. FEARON
    • 1
  • STEPHEN T. BROWN
    • 2
  • KRISTIN HUDASEK
    • 2
  • JASON L. SCRAGG
    • 3
  • JOHN P. BOYLE
    • 3
  • CHRIS PEERS
    • 3
  1. 1.Faculty of Life SciencesThe University of ManchesterManchesterUK
  2. 2.Department of BiologyMcMaster UniversityHamiltonCanada
  3. 3.School of MedicineThe University of LeedsLeedsUK

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