Barbara Pavan1, Antonio Capuzzo2, Giuseppe Forlani2. 1. Dept of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy. Electronic address: pvnbbr@unife.it. 2. Dept of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy.
Abstract
AIMS: The ability of the plant flavonol quercetin and its conjugated form quercetin-3-glucoside, compared to that of the anthocyanin cyanidin-3-glucoside, to interfere with 3',5'-cyclic adenosine monophosphate (cAMP) efflux was investigated in cultured human retinal pigment epithelial (HRPE) cells. MAIN METHODS: HRPE cells were stimulated for a time course with 1 μM adrenaline, in the presence and absence of increasing concentrations of anthocyanins or flavonols, then intracellular and extracellular cAMP levels obtained from whole cells and cAMP synthetized by the activity of adenylate cyclase in cell membrane fractions were determined by radiochemical assay. KEY FINDINGS: The treatment with either compound caused a significant lowering in extracellular cAMP concentrations deriving from a time course cell stimulation with 1 μM epinephrine. As to quercetin, the effect was shown to rely on the inhibition of cAMP efflux transporters. In the case of the glycoside, it was found to depend on the contrary on a reduction in the extent of epinephrine stimulation. Consistently, quercetin-3-glucoside inhibited the epinephrine-stimulated activity of adenylyl cyclase in membrane preparations, while quercetin was ineffective. The anthocyanin cyanidin-3-glucoside exerted similar effects as quercetin-3-glucoside. SIGNIFICANCE: Results strengthen the diverse effect of the glucosides versus the corresponding aglycones. Since differently from flavonols, anthocyanins are present in human plasma in their glycosylated form, the aglycone or glycoside forms of these plant secondary metabolites might therefore be utilized as synergistic regulators of cAMP homeostasis for therapeutical purposes.
AIMS: The ability of the plant flavonolquercetin and its conjugated form quercetin-3-glucoside, compared to that of the anthocyanin cyanidin-3-glucoside, to interfere with 3',5'-cyclic adenosine monophosphate (cAMP) efflux was investigated in cultured human retinal pigment epithelial (HRPE) cells. MAIN METHODS: HRPE cells were stimulated for a time course with 1 μM adrenaline, in the presence and absence of increasing concentrations of anthocyanins or flavonols, then intracellular and extracellular cAMP levels obtained from whole cells and cAMP synthetized by the activity of adenylate cyclase in cell membrane fractions were determined by radiochemical assay. KEY FINDINGS: The treatment with either compound caused a significant lowering in extracellular cAMP concentrations deriving from a time course cell stimulation with 1 μM epinephrine. As to quercetin, the effect was shown to rely on the inhibition of cAMP efflux transporters. In the case of the glycoside, it was found to depend on the contrary on a reduction in the extent of epinephrine stimulation. Consistently, quercetin-3-glucoside inhibited the epinephrine-stimulated activity of adenylyl cyclase in membrane preparations, while quercetin was ineffective. The anthocyanin cyanidin-3-glucoside exerted similar effects as quercetin-3-glucoside. SIGNIFICANCE: Results strengthen the diverse effect of the glucosides versus the corresponding aglycones. Since differently from flavonols, anthocyanins are present in human plasma in their glycosylated form, the aglycone or glycoside forms of these plant secondary metabolites might therefore be utilized as synergistic regulators of cAMP homeostasis for therapeutical purposes.
Authors: Dominique R Perez; Larry A Sklar; Alexandre Chigaev; Ksenia Matlawska-Wasowska Journal: Semin Cancer Biol Date: 2020-02-07 Impact factor: 15.707