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A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and Amyloid Beta 40 Peptides, Capable of Oligomer Formation
Published on: March 27, 2017
Amyloid-beta Interactions with ABC Transporters and Resistance Modifiers
Joseph Molnar1, Imre Ocsovszki2, Rozalia Pusztai3
1Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary molnar.jozsef@med.u-szeged.hu.
Amyloid-beta complexes with ABC transporter inhibitors reduced multidrug resistance in tumor cells by inhibiting efflux pumps. This suggests a potential link between reduced membrane transport and lower cancer incidence in Alzheimer's disease.
Area of Science:
- Biochemistry
- Oncology
- Neuroscience
Background:
- Multidrug resistance (MDR) in cancer is mediated by ATP-binding cassette (ABC) transporters, hindering chemotherapy efficacy.
- Similar ABC transporters are involved in clearing amyloid deposits in Alzheimer's disease (AD).
Purpose of the Study:
- To investigate the effects of amyloid-beta complexes with ABC transporter inhibitors on MDR tumor cells.
- To assess the potential of these complexes in reversing multidrug resistance and inducing apoptosis.
Main Methods:
- Rhodamine-123 accumulation was used to measure efflux pump activity in treated MDR cells.
- Annexin-V and propidium iodide staining assessed apoptosis induction.
- Flow cytometry (PARTEC FACScan) analyzed cellular fluorescence.
Main Results:
- Disiloxanes and memantine complexed with amyloid-beta 1-42 decreased ABC transporter activity in MDR tumor cells.
- Amyloid-beta complexes moderately increased early apoptosis.
- No significant changes were observed in late apoptosis or total viable cell count.
Conclusions:
- Amyloid-beta and its complexes inactivate tumor cell efflux pumps, leading to amyloid accumulation.
- Reduced membrane transport activity may contribute to the observed lower cancer incidence in Alzheimer's disease patients.
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