Oxygen Concentration and Oxidative Stress Modulate the Influence of Alzheimer’s Disease Aβ1–42 Peptide on Human Cells

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.

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