Multidrug and Toxic Compound Extrusion Protein‑1 (MATE1/SLC47A1) Is a Novel Flavonoid Transporter
Dietary flavonoids have various biological functions. However, their cellular transport mechanisms are largely unknown. We have determined that the multidrug and toxic compound extrusion transporter-1 (MATE1) is a membrane transporter for flavonoids and has a high affinity for quercetin. HEK293T cel...
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2014-10, Vol.62 (40), p.9690-9698 |
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| container_title | Journal of agricultural and food chemistry |
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| creator | Lee, Ji Hae Lee, Jung Eun Kim, Yeojin Lee, Hojoung Jun, Hee-jin Lee, Sung-Joon |
| description | Dietary flavonoids have various biological functions. However, their cellular transport mechanisms are largely unknown. We have determined that the multidrug and toxic compound extrusion transporter-1 (MATE1) is a membrane transporter for flavonoids and has a high affinity for quercetin. HEK293T cells overexpressing MATE1 exhibited increased intracellular quercetin accumulation. This effect disappeared in the presence of a MATE1 inhibitor and after MATE1 gene knockdown. HepG2 cells expressed MATE1 significantly, with the uptake quercetin of which was dramatically reduced with MATE1 inhibition. On the basis of immunofluorescence analysis, MATE1 was highly expressed in peroxisomes and the endoplasmic reticulum (ER) as well as in plasma membranes in the liver and intestine, which suggests potential accumulation of quercetin in peroxisomes and the ER in these tissues. Fluorescent microscopic analysis confirmed selective accumulation of qurcetin in peroxisome. The effects of quercetin on cellular lipid reduction and glucose uptake were exaggerated with MATE1 overexpression. In conclusion, MATE1 is a membrane transporter for quercetin; its overexpression enhances the hypolipidemic activity of quercetin and cellular glucose transport. Considering the low bioavailability of quercetin, appropriate regulation of MATE1 expression may optimize cellular quercetin concentrations and promote health benefits. |
| doi_str_mv | 10.1021/jf500916d |
| format | Article |
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However, their cellular transport mechanisms are largely unknown. We have determined that the multidrug and toxic compound extrusion transporter-1 (MATE1) is a membrane transporter for flavonoids and has a high affinity for quercetin. HEK293T cells overexpressing MATE1 exhibited increased intracellular quercetin accumulation. This effect disappeared in the presence of a MATE1 inhibitor and after MATE1 gene knockdown. HepG2 cells expressed MATE1 significantly, with the uptake quercetin of which was dramatically reduced with MATE1 inhibition. On the basis of immunofluorescence analysis, MATE1 was highly expressed in peroxisomes and the endoplasmic reticulum (ER) as well as in plasma membranes in the liver and intestine, which suggests potential accumulation of quercetin in peroxisomes and the ER in these tissues. Fluorescent microscopic analysis confirmed selective accumulation of qurcetin in peroxisome. The effects of quercetin on cellular lipid reduction and glucose uptake were exaggerated with MATE1 overexpression. In conclusion, MATE1 is a membrane transporter for quercetin; its overexpression enhances the hypolipidemic activity of quercetin and cellular glucose transport. Considering the low bioavailability of quercetin, appropriate regulation of MATE1 expression may optimize cellular quercetin concentrations and promote health benefits.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/jf500916d</identifier><identifier>PMID: 25241911</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; bioavailability ; Biological Transport ; Cells, Cultured ; endoplasmic reticulum ; Endoplasmic Reticulum - metabolism ; extrusion ; Flavonoids - metabolism ; Flavonoids - pharmacokinetics ; fluorescence ; fluorescent antibody technique ; Gene Knockdown Techniques ; genes ; glucose ; HEK293 Cells ; Hep G2 Cells - drug effects ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; human cell lines ; Humans ; Intestinal Mucosa - metabolism ; intestines ; lipids ; liver ; Liver - metabolism ; Mice ; Organic Cation Transport Proteins - genetics ; Organic Cation Transport Proteins - metabolism ; peroxisomes ; Peroxisomes - metabolism ; plasma membrane ; quercetin ; Quercetin - metabolism ; Quercetin - pharmacokinetics ; tissues ; toxic substances</subject><ispartof>Journal of agricultural and food chemistry, 2014-10, Vol.62 (40), p.9690-9698</ispartof><rights>Copyright © 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a405t-45e3ab9da07212e356d8190c2eec89dbe9d5b6e2c52cd2ef59644f7283919a763</citedby><cites>FETCH-LOGICAL-a405t-45e3ab9da07212e356d8190c2eec89dbe9d5b6e2c52cd2ef59644f7283919a763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jf500916d$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jf500916d$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25241911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Ji Hae</creatorcontrib><creatorcontrib>Lee, Jung Eun</creatorcontrib><creatorcontrib>Kim, Yeojin</creatorcontrib><creatorcontrib>Lee, Hojoung</creatorcontrib><creatorcontrib>Jun, Hee-jin</creatorcontrib><creatorcontrib>Lee, Sung-Joon</creatorcontrib><title>Multidrug and Toxic Compound Extrusion Protein‑1 (MATE1/SLC47A1) Is a Novel Flavonoid Transporter</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Dietary flavonoids have various biological functions. However, their cellular transport mechanisms are largely unknown. We have determined that the multidrug and toxic compound extrusion transporter-1 (MATE1) is a membrane transporter for flavonoids and has a high affinity for quercetin. HEK293T cells overexpressing MATE1 exhibited increased intracellular quercetin accumulation. This effect disappeared in the presence of a MATE1 inhibitor and after MATE1 gene knockdown. HepG2 cells expressed MATE1 significantly, with the uptake quercetin of which was dramatically reduced with MATE1 inhibition. On the basis of immunofluorescence analysis, MATE1 was highly expressed in peroxisomes and the endoplasmic reticulum (ER) as well as in plasma membranes in the liver and intestine, which suggests potential accumulation of quercetin in peroxisomes and the ER in these tissues. Fluorescent microscopic analysis confirmed selective accumulation of qurcetin in peroxisome. The effects of quercetin on cellular lipid reduction and glucose uptake were exaggerated with MATE1 overexpression. In conclusion, MATE1 is a membrane transporter for quercetin; its overexpression enhances the hypolipidemic activity of quercetin and cellular glucose transport. Considering the low bioavailability of quercetin, appropriate regulation of MATE1 expression may optimize cellular quercetin concentrations and promote health benefits.</description><subject>Animals</subject><subject>bioavailability</subject><subject>Biological Transport</subject><subject>Cells, Cultured</subject><subject>endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>extrusion</subject><subject>Flavonoids - metabolism</subject><subject>Flavonoids - pharmacokinetics</subject><subject>fluorescence</subject><subject>fluorescent antibody technique</subject><subject>Gene Knockdown Techniques</subject><subject>genes</subject><subject>glucose</subject><subject>HEK293 Cells</subject><subject>Hep G2 Cells - drug effects</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>human cell lines</subject><subject>Humans</subject><subject>Intestinal Mucosa - metabolism</subject><subject>intestines</subject><subject>lipids</subject><subject>liver</subject><subject>Liver - metabolism</subject><subject>Mice</subject><subject>Organic Cation Transport Proteins - genetics</subject><subject>Organic Cation Transport Proteins - metabolism</subject><subject>peroxisomes</subject><subject>Peroxisomes - metabolism</subject><subject>plasma membrane</subject><subject>quercetin</subject><subject>Quercetin - metabolism</subject><subject>Quercetin - pharmacokinetics</subject><subject>tissues</subject><subject>toxic substances</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0MFOwkAQBuCN0SiiB19A92Iih8rMttt2j4SAkoCaAOdm292SktIluy3Bm6_gK_ok1qCcPE0m82Um8xNyg_CIwLC_zjmAwFCdkA5yBh5HjE9JB9qhF_MQL8ilc2sAiHkE5-SCcRagQOyQbNaUdaFss6KyUnRh9kVGh2azNU3bjva1bVxhKvpmTa2L6uvjE-nDbLAYYX8-HQbRAHt04qikL2anSzou5c5Upmg3WVm5rbG1tlfkLJel09e_tUuW49Fi-OxNX58mw8HUkwHw2gu49mUqlISIIdM-D1WMAjKmdRYLlWqheBpqlnGWKaZzLsIgyCMW-wKFjEK_S3qHvZk1zlmdJ1tbbKR9TxCSn6CSY1CtvT3YbZNutDrKv2RacHcAuTSJXNnCJcs5AwwBkEHgx624PwiZuWRtGlu1z_1z6huL1XeQ</recordid><startdate>20141008</startdate><enddate>20141008</enddate><creator>Lee, Ji Hae</creator><creator>Lee, Jung Eun</creator><creator>Kim, Yeojin</creator><creator>Lee, Hojoung</creator><creator>Jun, Hee-jin</creator><creator>Lee, Sung-Joon</creator><general>American Chemical Society</general><general>American Chemical Society, Books and Journals Division</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20141008</creationdate><title>Multidrug and Toxic Compound Extrusion Protein‑1 (MATE1/SLC47A1) Is a Novel Flavonoid Transporter</title><author>Lee, Ji Hae ; Lee, Jung Eun ; Kim, Yeojin ; Lee, Hojoung ; Jun, Hee-jin ; Lee, Sung-Joon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a405t-45e3ab9da07212e356d8190c2eec89dbe9d5b6e2c52cd2ef59644f7283919a763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>bioavailability</topic><topic>Biological Transport</topic><topic>Cells, Cultured</topic><topic>endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>extrusion</topic><topic>Flavonoids - metabolism</topic><topic>Flavonoids - pharmacokinetics</topic><topic>fluorescence</topic><topic>fluorescent antibody technique</topic><topic>Gene Knockdown Techniques</topic><topic>genes</topic><topic>glucose</topic><topic>HEK293 Cells</topic><topic>Hep G2 Cells - drug effects</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>human cell lines</topic><topic>Humans</topic><topic>Intestinal Mucosa - metabolism</topic><topic>intestines</topic><topic>lipids</topic><topic>liver</topic><topic>Liver - metabolism</topic><topic>Mice</topic><topic>Organic Cation Transport Proteins - genetics</topic><topic>Organic Cation Transport Proteins - metabolism</topic><topic>peroxisomes</topic><topic>Peroxisomes - metabolism</topic><topic>plasma membrane</topic><topic>quercetin</topic><topic>Quercetin - metabolism</topic><topic>Quercetin - pharmacokinetics</topic><topic>tissues</topic><topic>toxic substances</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Ji Hae</creatorcontrib><creatorcontrib>Lee, Jung Eun</creatorcontrib><creatorcontrib>Kim, Yeojin</creatorcontrib><creatorcontrib>Lee, Hojoung</creatorcontrib><creatorcontrib>Jun, Hee-jin</creatorcontrib><creatorcontrib>Lee, Sung-Joon</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Ji Hae</au><au>Lee, Jung Eun</au><au>Kim, Yeojin</au><au>Lee, Hojoung</au><au>Jun, Hee-jin</au><au>Lee, Sung-Joon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multidrug and Toxic Compound Extrusion Protein‑1 (MATE1/SLC47A1) Is a Novel Flavonoid Transporter</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2014-10-08</date><risdate>2014</risdate><volume>62</volume><issue>40</issue><spage>9690</spage><epage>9698</epage><pages>9690-9698</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>Dietary flavonoids have various biological functions. However, their cellular transport mechanisms are largely unknown. We have determined that the multidrug and toxic compound extrusion transporter-1 (MATE1) is a membrane transporter for flavonoids and has a high affinity for quercetin. HEK293T cells overexpressing MATE1 exhibited increased intracellular quercetin accumulation. This effect disappeared in the presence of a MATE1 inhibitor and after MATE1 gene knockdown. HepG2 cells expressed MATE1 significantly, with the uptake quercetin of which was dramatically reduced with MATE1 inhibition. On the basis of immunofluorescence analysis, MATE1 was highly expressed in peroxisomes and the endoplasmic reticulum (ER) as well as in plasma membranes in the liver and intestine, which suggests potential accumulation of quercetin in peroxisomes and the ER in these tissues. Fluorescent microscopic analysis confirmed selective accumulation of qurcetin in peroxisome. The effects of quercetin on cellular lipid reduction and glucose uptake were exaggerated with MATE1 overexpression. In conclusion, MATE1 is a membrane transporter for quercetin; its overexpression enhances the hypolipidemic activity of quercetin and cellular glucose transport. Considering the low bioavailability of quercetin, appropriate regulation of MATE1 expression may optimize cellular quercetin concentrations and promote health benefits.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>25241911</pmid><doi>10.1021/jf500916d</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals bioavailability Biological Transport Cells, Cultured endoplasmic reticulum Endoplasmic Reticulum - metabolism extrusion Flavonoids - metabolism Flavonoids - pharmacokinetics fluorescence fluorescent antibody technique Gene Knockdown Techniques genes glucose HEK293 Cells Hep G2 Cells - drug effects Hepatocytes - drug effects Hepatocytes - metabolism human cell lines Humans Intestinal Mucosa - metabolism intestines lipids liver Liver - metabolism Mice Organic Cation Transport Proteins - genetics Organic Cation Transport Proteins - metabolism peroxisomes Peroxisomes - metabolism plasma membrane quercetin Quercetin - metabolism Quercetin - pharmacokinetics tissues toxic substances |
| title | Multidrug and Toxic Compound Extrusion Protein‑1 (MATE1/SLC47A1) Is a Novel Flavonoid Transporter |
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