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Liczba wyników
2013 | 73 | 1 |
Tytuł artykułu

Alzheimer’s amyloid beta peptides disturb circadian oscillations of intracellular calcium concentration

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
It is postulated that disturbances in calcium homeostasis play an important role in pathogenesis of Alzheimer’s disease (AD). Changes of neuronal calcium concentration are responsible for the oxidative stress as well as altered metabolism and production of amyloid-beta peptides (Aβ). Aβ may further exacerbate calcium dysregulation, causing synaptic dysfunction, neurodegeneration and cognitive impairment. Recent data indicate that AD is associated with disturbances of circadian rhythm in the patients. However, till now nothing is known about the molecular mechanisms involved in AD-related circadian clock alterations. In our study we investigated the effect of Aβ peptides on the rhythmic oscillation of cytosolic and mitochondrial calcium levels. To investigate molecular clock mechanisms, the studies we carried out in human primary skin fibroblasts, a previously established experimental model. Our data showed circadian rhythm of calcium ions concentration in cytosol and mitochondria. Moreover we observed circadian oscillation of ROS formation and redox potential. Treatment with Aβ fibrils at the concentration of 0.5 µM disturbed cytosolic calcium oscillations and mitochondrial redox state. Studying mechanisms involved in this phenomenon indicated that Aβ did not affect ER calcium stores, but induced changes of calcium influx mediated by purinergic P2X7 receptor. The specific antagonist of P2X7 receptor Brillant Blue G abolished negative impact of Aβ and restored calcium circadian rhythm. Summarizing, our results indicate that Aβ may play a significant role in disturbances of circadian calcium oscillation, suggesting the importance of this phenomenon in ADrelated changes in biological clock. Supported by grants from Sciex 10. 258 to A.K. as well as Swiss National foundation (SNF No 310030_122572) and Synapsis Foundation to A.E.
Wydawca
-
Rocznik
Tom
73
Numer
1
Opis fizyczny
p.189
Twórcy
  • Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland
  • Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
autor
  • Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland
autor
  • Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland
  • Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
autor
  • Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
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