Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter

Maestro, Alessandra; Terdoslavich, Michela; Vanzo, Andreja; Kuku, Adenike; Tramer, Federica; Nicolin, Vanessa; Micali, Fulvio; Decorti, Giuliana; Passamonti, Sabina

doi:10.1093/cvr/cvp290

Cited by 60 publications

(49 citation statements)

References 49 publications

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“…A limited number of studies that have focused mainly on anthocyanins have indicated that bilitranslocase may be involved in vascular epithelial and hepatic flavonoid uptakes and anthocyanin absorption from the stomach (46–49). However, the relative importance of bilitranslocase and the identity of other transporters remain to be established.…”

Section: Overview Of Flavonoid Metabolismmentioning

confidence: 99%

The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids

Cassidy

Minihane

2017

The American Journal of Clinical Nutrition

393

287

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At a population level, there is growing evidence of the beneficial effects of dietary flavonoids on health. However, there is extensive heterogeneity in the response to increased intake, which is likely mediated via wide interindividual variability in flavonoid absorption and metabolism. Flavonoids are extensively metabolized by phase I and phase II metabolism (which occur predominantly in the gastrointestinal tract and liver) and colonic microbial metabolism. A number of factors, including age, sex, and genotype, may affect these metabolic processes. In addition, food composition and flavonoid source are likely to affect bioavailability, and emerging data suggest a critical role for the microbiome. This review will focus on the current knowledge for the main subclasses of flavonoids, including anthocyanins, flavonols, flavan-3-ols, and flavanones, for which there is growing evidence from prospective studies of beneficial effects on health. The identification of key factors that govern metabolism and an understanding of how the differential capacity to metabolize these bioactive compounds affect health outcomes will help establish how to optimize intakes of flavonoids for health benefits and in specific subgroups. We identify research areas that need to be addressed to further understand important determinants of flavonoid bioavailability and metabolism and to advance the knowledge base that is required to move toward the development of dietary guidelines and recommendations for flavonoids and flavonoid-rich foods.

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Section: Overview Of Flavonoid Metabolismmentioning

confidence: 99%

The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids

Cassidy

Minihane

2017

The American Journal of Clinical Nutrition

393

287

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“…This is an unusual finding without clear explanation. In addition to liver, bilitranslocase has been described as present in vascular endothelium, heart, intestinal epithelium, kidney, as well as in plants including carnation petals and grapes (14, 109). The physiological role of bilitranslocase in organic anion transport will require additional clarification.…”

Section: Clearance Of Organic Anions From the Circulationmentioning

confidence: 99%

Organic Anion Uptake by Hepatocytes

Wolkoff

2014

Comprehensive Physiology

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Many of the compounds taken up by the liver are organic anions that circulate tightly bound to protein carriers such as albumin. The fenestrated sinusoidal endothelium of the liver permits these compounds to have access to hepatocytes. Studies to characterize hepatic uptake of organic anions through kinetic analyses, suggested that it was carrier-mediated. Attempts to identify specific transporters by biochemical approaches were largely unsuccessful and were replaced by studies that utilized expression cloning. These studies led to identification of the organic anion transport proteins (oatps), a family of 12 transmembrane domain glycoproteins that have broad and often overlapping substrate specificities. The oatps mediate Na+-independent organic anion uptake. Other studies identified a seven transmembrane domain glycoprotein, Na+/taurocholate transporting protein (ntcp) as mediating Na+-dependent uptake of bile acids as well as other organic anions. Although mutations or deficiencies of specific members of the oatp family have been associated with transport abnormalities, there have been no such reports for ntcp, and its physiologic role remains to be determined, although expression of ntcp in vitro recapitulates the characteristics of Na+-dependent bile acid transport that is seen in vivo. Both ntcp and oatps traffic between the cell surface and intracellular vesicular pools. These vesicles move through the cell on microtubules, using the microtubule based motors dynein and kinesins. Factors that regulate this motility are under study and may provide a unique mechanism that can alter the plasma membrane content of these transporters and consequently their accessibility to circulating ligands.

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“…In fact, we have found that a very low concentration of cyanidin 3-glucoside induces nitric oxide-dependent vasorelaxation of rat aortic rings (Ziberna et al, 2011). The enzyme (e-NOS, a synthase) catalysing the formation of nitric oxide is activated by cyanidin 3-glucoside (Xu et al, 2004), which would enter into the cells via bilitranslocase (Maestro et al, 2010). Indeed, pre-treatment of rat aortic rings with purified anti-sequence bilitranslocase antibodies blunted cyanidin 3-glucoside-induced vasorelaxation (Ziberna et al, 2011).…”

Section: The Expression Of Bilitranslocase In the Vascular Endotheliumentioning

confidence: 93%

“…Here, some flavonoids, including malvidin 3-glucoside, have been found to enter into cells via bilitranslocase (Maestro et al, 2010). The vascular endothelium in humans forms a surface of 240 m 2 , thus representing one of the major targets of flavonoids.…”

Section: The Expression Of Bilitranslocase In the Vascular Endotheliumentioning

confidence: 99%

Wine Pigments: From Your Cup to Your Cells

Passamonti

Vanzo

Tramer

et al. 2011

Journal of Wine Research

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Anthocyanins are among the various bioactive components of wines to which health- promoting effects are ascribed. Their bioavailability is however very limited, as shown by post- absorption plasma concentration values of 10-9–10-8 M. The cardiovascular system is one of the main targets of anthocyanin bioactivity. The presence of the membrane transporter bilitranslocase (T.C. 2.A.65.1.1) in the vascular endothelium allows the transport of wine anthocyanins from the blood into the cells. Here anthocyanins can trigger further biological responses, ending with the release of nitric oxide, a powerful factor of cardiovascular protection

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Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter

Abstract: The uptake of some flavonoids into the vascular endothelium occurs via the bilirubin-specific membrane transporter bilitranslocase. This offers new insights into the vascular effects of both flavonoids and bilirubin.

Cited by 60 publications

References 49 publications

The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids

The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids

Organic Anion Uptake by Hepatocytes

Wine Pigments: From Your Cup to Your Cells

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