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Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

Wright B, Gibson T, Spencer J, Lovegrove JA, Gibbins JM - PLoS ONE (2010)

Bottom Line: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue.It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function.High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom. b.wright@rdg.ac.uk

ABSTRACT

Background: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function.

Methodology/principal findings: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets.

Conclusions/significance: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds.

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Related in: MedlinePlus

Platelets internalise quercetin and tamarixetin.Platelets suspended to a density of 2×108 cells.mL−1 were incubated with quercetin (100 µM: (B.i-iii) and (C.i-iii)), tamarixetin (40 µM: (D.i-iii) and (E.i-iii)) or solvent control (DMSO (0.2% (v/v)): (A.i-iii)) for 30 min. Fluorescence was detected at 480 nm–500 nm after excitation at 430 nm with an argon laser. Images of a single middle layer from z-stacks are shown (DMSO control: (A.i-iii), quercetin: (B.i-iii) tamarixetin: (C.i-iii)) and higher magnifications of areas of interest are also shown (quercetin: (D.i-iii), tamarixetin: (E.i-iii)). Images represent results from at least 3 individual experiments.
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pone-0009673-g002: Platelets internalise quercetin and tamarixetin.Platelets suspended to a density of 2×108 cells.mL−1 were incubated with quercetin (100 µM: (B.i-iii) and (C.i-iii)), tamarixetin (40 µM: (D.i-iii) and (E.i-iii)) or solvent control (DMSO (0.2% (v/v)): (A.i-iii)) for 30 min. Fluorescence was detected at 480 nm–500 nm after excitation at 430 nm with an argon laser. Images of a single middle layer from z-stacks are shown (DMSO control: (A.i-iii), quercetin: (B.i-iii) tamarixetin: (C.i-iii)) and higher magnifications of areas of interest are also shown (quercetin: (D.i-iii), tamarixetin: (E.i-iii)). Images represent results from at least 3 individual experiments.

Mentions: To determine whether quercetin and tamarixetin were able to gain access to the platelet cytosol containing metabolic enzymes, the intrinsic fluorescent properties of quercetin and tamarixetin [27] were utilised to visualise their potential presence within these cells. Following incubation with quercetin (100 µM), tamarixetin (40 µM) or the solvent control, dimethylsulphoxide (DMSO: 0.2% (v/v)) for 30 min, a series of images in the z dimension were obtained at 0.2 µm intervals through the membrane and cytosol of platelets. A single image of a layer from the middle of the series illustrated internalisation of quercetin (Figure 2B. i-iii and 2C. i-iii) and tamarixetin (Figure 2D. i-iii and 2E. i-iii) and magnified images showed greater detail (quercetin: Figure 2C. i-iii) and (tamarixetin: Figure 2E. i-iii). Low levels of auto-fluorescence were detected in untreated platelets (Figure 2A.i-iii).


Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

Wright B, Gibson T, Spencer J, Lovegrove JA, Gibbins JM - PLoS ONE (2010)

Platelets internalise quercetin and tamarixetin.Platelets suspended to a density of 2×108 cells.mL−1 were incubated with quercetin (100 µM: (B.i-iii) and (C.i-iii)), tamarixetin (40 µM: (D.i-iii) and (E.i-iii)) or solvent control (DMSO (0.2% (v/v)): (A.i-iii)) for 30 min. Fluorescence was detected at 480 nm–500 nm after excitation at 430 nm with an argon laser. Images of a single middle layer from z-stacks are shown (DMSO control: (A.i-iii), quercetin: (B.i-iii) tamarixetin: (C.i-iii)) and higher magnifications of areas of interest are also shown (quercetin: (D.i-iii), tamarixetin: (E.i-iii)). Images represent results from at least 3 individual experiments.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2837383&req=5

pone-0009673-g002: Platelets internalise quercetin and tamarixetin.Platelets suspended to a density of 2×108 cells.mL−1 were incubated with quercetin (100 µM: (B.i-iii) and (C.i-iii)), tamarixetin (40 µM: (D.i-iii) and (E.i-iii)) or solvent control (DMSO (0.2% (v/v)): (A.i-iii)) for 30 min. Fluorescence was detected at 480 nm–500 nm after excitation at 430 nm with an argon laser. Images of a single middle layer from z-stacks are shown (DMSO control: (A.i-iii), quercetin: (B.i-iii) tamarixetin: (C.i-iii)) and higher magnifications of areas of interest are also shown (quercetin: (D.i-iii), tamarixetin: (E.i-iii)). Images represent results from at least 3 individual experiments.
Mentions: To determine whether quercetin and tamarixetin were able to gain access to the platelet cytosol containing metabolic enzymes, the intrinsic fluorescent properties of quercetin and tamarixetin [27] were utilised to visualise their potential presence within these cells. Following incubation with quercetin (100 µM), tamarixetin (40 µM) or the solvent control, dimethylsulphoxide (DMSO: 0.2% (v/v)) for 30 min, a series of images in the z dimension were obtained at 0.2 µm intervals through the membrane and cytosol of platelets. A single image of a layer from the middle of the series illustrated internalisation of quercetin (Figure 2B. i-iii and 2C. i-iii) and tamarixetin (Figure 2D. i-iii and 2E. i-iii) and magnified images showed greater detail (quercetin: Figure 2C. i-iii) and (tamarixetin: Figure 2E. i-iii). Low levels of auto-fluorescence were detected in untreated platelets (Figure 2A.i-iii).

Bottom Line: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue.It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function.High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom. b.wright@rdg.ac.uk

ABSTRACT

Background: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function.

Methodology/principal findings: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets.

Conclusions/significance: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds.

Show MeSH
Related in: MedlinePlus