| Flavonoids are a large group of phytochemicals, which belong to the class/category of polyphenols. They are omnipresent in the human diet and are found in fruits, vegetables and grains Flavonoids in food are generally considered to be beneficial to consumers' health and are one of the most important categories of bioactive food components [1]. Epidemiological observations ascribed flavonoids to be preventive in coronary heart disease, stroke and certain cancers. The health-protective effect of bioactive compounds is considerd to be accomplished by several mechanisms including modulation of the activity of enzyme systems responsible for deactivation of chemical carcinogens, such as NAD(P)H:quinone oxidoreductase 1 (NQO1; EC 1.6.99.2) NQO1 catalyses the two- or four electron reduction of quinones by which the formation of toxic semiquinone radicals (formed upon transfer of one electron) can be suppressed. The hydroquinone products can more readily be conjugated and excreted by the organism. NQO1 and flavonoids, both supposed to be health- promoting factors, have a complex interplay. Several flavonoids act as NQO1 inducers by activating its transcription through the electrophile-responsive-element (EpRE), while on the other hand some of them can act as inhibitors of the enzyme activity. This project is a collaboration between the departments of Biochemistry and Toxicology. We aim to elucidate the complex interplay between NQO1 and flavonoids in human cells. In the past several methods have been developed to determine NQO1 activity. However, most of the substrates used react with a broad range of enzymes. Data obtained with different substrates are difficult to compare and do not necessarily represent the NQO1 expression in the intact cell. Initial investigations during this project have led to the development of a new method for evaluation of intracellular NQO1 activity using a fluorescent substrate that can be measured in the intact cell. |
