Peroxynitrite and 4-Hydroxynonenal Inactivate Breast Cancer Resistance Protein/ABCG2

Oxidative stress may arise from a variety of pathologies and results in the formation of toxic and reactive chemical species. Extensive research has been done to establish mechanisms of formation and cytotoxic effects of a number of different products of oxidation stress including peroxynitrite (PN)...

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Bibliographic Details
Published in:BioMed research international 2019-01, Vol.2019 (2019), p.1-6
Main Authors: Verenich, Svetlana, Gerk, Phillip M.
Format: Article
Language:English
Subjects:
4-Hydroxynonenal
ABC transporters
Bile
Breast cancer
Chemical speciation
Cytotoxicity
Diabetes
Experiments
Lipid peroxidation
Lipids
Membrane vesicles
Metabolism
Organic chemistry
Oxidation
Oxidation resistance
Oxidative stress
Peroxynitrite
Physiology
Proteins
Riboflavin
Substrates
Sucrose
Transport
Variance analysis
Vesicles
Vitamin B
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Summary:Oxidative stress may arise from a variety of pathologies and results in the formation of toxic and reactive chemical species. Extensive research has been done to establish mechanisms of formation and cytotoxic effects of a number of different products of oxidation stress including peroxynitrite (PN) and 4-hydroxynonenal (4HNE). However, relatively few studies have investigated their effects on ATP-binding cassette (ABC) transporters. The objective of this investigation was to determine the effects of PN and 4HNE on BCRP/ABCG2. To eliminate the effect of metabolic enzymes, the experiments were carried out with inside-out Sf9 membrane vesicles overexpressing BCRP/ABCG2 using riboflavin as a substrate. The experiments revealed that PN produced IC50 of about 31.2 ± 2.7 μM, based upon initial concentrations. The IC50 for 4HNE was estimated to be 92 ± 1.4 μM. Preincubation of membrane vesicles with either PN or 4HNE caused the maximal rate of transport (Vmax) to drop drastically, up to 19 times, with no or much smaller effect on Km. Thus, PN and 4NE can inhibit BCRP transport activity.
ISSN:2314-6133
2314-6141
DOI:10.1155/2019/3891535