Oxygen Concentration and Oxidative Stress Modulate the Influence of Alzheimer's Disease A β1-42 Peptide on Human Cells

Oxid Med Cell Longev. 2018 Jan 11;2018:7567959. doi: 10.1155/2018/7567959. eCollection 2018.

Abstract

Reactive oxygen species (ROS) generated after exposure to ionizing radiation and toxic peptides, in mitochondrial metabolism and during aging contribute to damage of cell's structural and functional components and can lead to diseases. Monomers and small oligomers of amyloid beta (Aβ) peptide, players in Alzheimer's disease, are recently suggested to be involved in damaging of neurons, instead of extracellular Aβ plaques. We demonstrate that externally applied disaggregated Aβ1-42 peptide interacts preferentially with acidic compartments (lysosomes). We compared standard cell cultivation (21% O2) to more physiological cell cultivation (5% O2). Cells did not exhibit a dramatic increase in ROS and change in glutathione level upon 4 μM Aβ peptide treatment, whereas exposure to 2 Gy X-rays increased ROS and changed glutathione level and ATP concentration. The occurrence of the 4977 bp deletion in mtDNA and significant protein carbonylation were specific effects of IR and more pronounced at 21% O2. An increase in cell death after Aβ peptide treatment or irradiation was unexpectedly restored to the control level or below when both were combined, particularly at 5% O2. Therefore, Aβ peptide at low concentration can trigger neuroprotective mechanisms in cells exposed to radiation. Oxygen concentration is an important modulator of cellular responses to stress.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacokinetics
  • Animals
  • Cell Line, Tumor
  • Humans
  • Inflammation / metabolism
  • Mice
  • Oxidative Stress / physiology*
  • Oxygen / metabolism*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacokinetics

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Oxygen