Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport
Sodium-hydrogen exchanger regulatory factor-1-deficient (NHERF-1(-/-)) mice demonstrate increases in the urinary excretion of phosphate, calcium, and uric acid associated with interstitial deposition of calcium in the papilla of the kidney. These studies examine the role of NHERF-1 in the tubular re...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2007-05, Vol.18 (5), p.1419-1425 |
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| creator | CUNNINGHAM, Rochelle BRAZIE, Marc SHENOLIKAR, Shirish WEINMAN, Edward J KANUMURU, Srilatha XIAOFEI E BISWAS, Rajat FENGYING WANG STEPLOCK, Deborah WADE, James B ANZAI, Naohiko ENDOU, Hitoshi |
| description | Sodium-hydrogen exchanger regulatory factor-1-deficient (NHERF-1(-/-)) mice demonstrate increases in the urinary excretion of phosphate, calcium, and uric acid associated with interstitial deposition of calcium in the papilla of the kidney. These studies examine the role of NHERF-1 in the tubular reabsorption of uric acid and regulation of mouse urate transporter 1 (mURAT1), a newly described transporter that is responsible for the renal tubular reabsorption of uric acid. In primary cultures of mouse renal proximal tubule cells, uric acid uptake was significantly lower in NHERF-1(-/-) cells compared with wild-type cells over a large range of uric acid concentrations in the media. Western immunoblotting revealed a 56 +/- 6% decrease in the brush border membrane (BBM) expression of mURAT1 in NHERF-1(-/-) compared with wild-type control kidneys (P < 0.05). Confocal microscopy confirmed the reduced apical membrane expression of mURAT1 in NHERF-1(-/-) kidneys and demonstrated mislocalization of mURAT1 to intracellular vesicular structures. Para-aminohippurate significantly inhibited uric acid uptake in wild-type cells (41 +/- 2%) compared with NHERF-1(-/-) cells (8.2 +/- 3%). Infection of NHERF-1(-/-) cells with adenovirus-green fluorescence protein-NHERF-1 resulted in significantly higher rates of uric acid transport (15.4 +/- 1.1 pmol/microg protein per 30 min) compared with null cells that were infected with control adenovirus-green fluorescence protein (7.9 +/- 0.3) and restoration of the inhibitory effect of para-aminohippurate (% inhibition 34 +/- 4%). These findings indicate that NHERF-1 exerts a significant effect on the renal tubular reabsorption of uric acid in the mouse by modulating the BBM abundance of mURAT1 and possibly other BBM uric acid transporters. |
| doi_str_mv | 10.1681/ASN.2006090980 |
| format | Article |
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These studies examine the role of NHERF-1 in the tubular reabsorption of uric acid and regulation of mouse urate transporter 1 (mURAT1), a newly described transporter that is responsible for the renal tubular reabsorption of uric acid. In primary cultures of mouse renal proximal tubule cells, uric acid uptake was significantly lower in NHERF-1(-/-) cells compared with wild-type cells over a large range of uric acid concentrations in the media. Western immunoblotting revealed a 56 +/- 6% decrease in the brush border membrane (BBM) expression of mURAT1 in NHERF-1(-/-) compared with wild-type control kidneys (P < 0.05). Confocal microscopy confirmed the reduced apical membrane expression of mURAT1 in NHERF-1(-/-) kidneys and demonstrated mislocalization of mURAT1 to intracellular vesicular structures. Para-aminohippurate significantly inhibited uric acid uptake in wild-type cells (41 +/- 2%) compared with NHERF-1(-/-) cells (8.2 +/- 3%). Infection of NHERF-1(-/-) cells with adenovirus-green fluorescence protein-NHERF-1 resulted in significantly higher rates of uric acid transport (15.4 +/- 1.1 pmol/microg protein per 30 min) compared with null cells that were infected with control adenovirus-green fluorescence protein (7.9 +/- 0.3) and restoration of the inhibitory effect of para-aminohippurate (% inhibition 34 +/- 4%). These findings indicate that NHERF-1 exerts a significant effect on the renal tubular reabsorption of uric acid in the mouse by modulating the BBM abundance of mURAT1 and possibly other BBM uric acid transporters.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/ASN.2006090980</identifier><identifier>PMID: 17409311</identifier><identifier>CODEN: JASNEU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Cell Membrane - metabolism ; Cells, Cultured ; Kidney Tubules, Proximal - metabolism ; Male ; Medical sciences ; Membrane Proteins - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microvilli - metabolism ; Nephrology. Urinary tract diseases ; Organic Anion Transporters - metabolism ; Phosphoproteins - genetics ; Phosphoproteins - metabolism ; Phosphoproteins - physiology ; Protein Binding ; Sodium-Hydrogen Exchangers - genetics ; Sodium-Hydrogen Exchangers - metabolism ; Sodium-Hydrogen Exchangers - physiology ; Transfection ; Uric Acid - metabolism</subject><ispartof>Journal of the American Society of Nephrology, 2007-05, Vol.18 (5), p.1419-1425</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c363t-c26451c3ecaabe6339d01a57f001f62787bd24d089dfa150b139eca714155f1d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18737460$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17409311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CUNNINGHAM, Rochelle</creatorcontrib><creatorcontrib>BRAZIE, Marc</creatorcontrib><creatorcontrib>SHENOLIKAR, Shirish</creatorcontrib><creatorcontrib>WEINMAN, Edward J</creatorcontrib><creatorcontrib>KANUMURU, Srilatha</creatorcontrib><creatorcontrib>XIAOFEI E</creatorcontrib><creatorcontrib>BISWAS, Rajat</creatorcontrib><creatorcontrib>FENGYING WANG</creatorcontrib><creatorcontrib>STEPLOCK, Deborah</creatorcontrib><creatorcontrib>WADE, James B</creatorcontrib><creatorcontrib>ANZAI, Naohiko</creatorcontrib><creatorcontrib>ENDOU, Hitoshi</creatorcontrib><title>Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>Sodium-hydrogen exchanger regulatory factor-1-deficient (NHERF-1(-/-)) mice demonstrate increases in the urinary excretion of phosphate, calcium, and uric acid associated with interstitial deposition of calcium in the papilla of the kidney. These studies examine the role of NHERF-1 in the tubular reabsorption of uric acid and regulation of mouse urate transporter 1 (mURAT1), a newly described transporter that is responsible for the renal tubular reabsorption of uric acid. In primary cultures of mouse renal proximal tubule cells, uric acid uptake was significantly lower in NHERF-1(-/-) cells compared with wild-type cells over a large range of uric acid concentrations in the media. Western immunoblotting revealed a 56 +/- 6% decrease in the brush border membrane (BBM) expression of mURAT1 in NHERF-1(-/-) compared with wild-type control kidneys (P < 0.05). Confocal microscopy confirmed the reduced apical membrane expression of mURAT1 in NHERF-1(-/-) kidneys and demonstrated mislocalization of mURAT1 to intracellular vesicular structures. Para-aminohippurate significantly inhibited uric acid uptake in wild-type cells (41 +/- 2%) compared with NHERF-1(-/-) cells (8.2 +/- 3%). Infection of NHERF-1(-/-) cells with adenovirus-green fluorescence protein-NHERF-1 resulted in significantly higher rates of uric acid transport (15.4 +/- 1.1 pmol/microg protein per 30 min) compared with null cells that were infected with control adenovirus-green fluorescence protein (7.9 +/- 0.3) and restoration of the inhibitory effect of para-aminohippurate (% inhibition 34 +/- 4%). These findings indicate that NHERF-1 exerts a significant effect on the renal tubular reabsorption of uric acid in the mouse by modulating the BBM abundance of mURAT1 and possibly other BBM uric acid transporters.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microvilli - metabolism</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Organic Anion Transporters - metabolism</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphoproteins - physiology</subject><subject>Protein Binding</subject><subject>Sodium-Hydrogen Exchangers - genetics</subject><subject>Sodium-Hydrogen Exchangers - metabolism</subject><subject>Sodium-Hydrogen Exchangers - physiology</subject><subject>Transfection</subject><subject>Uric Acid - metabolism</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtPwzAQhC0EolC4ckS-wC1lN07s5FhVvKQKDoVz5NhOG5RHsR3R_gd-NK5a1NPOSt-sdoaQG4QJ8gwfpou3SQzAIYc8gxNygSljEUtSOA0aEh5xLtiIXDr3BYBpLMQ5GaFIIGeIF-R30et6aKPVVtt-aTpqNmolu6Wx1Jrl0Ejf2y2tpAozQlp33tiwOPpT-xVt-8EZOljpDfVWdm7d2wBQpL7_95sgOtnQte03dRuEH8qh2blqRaWq9dF5Rc4q2ThzfZhj8vn0-DF7iebvz6-z6TxSjDMfqZgnKSpmlJSl4YzlGlCmogoBKx6LTJQ6TjRkua4kplAiywMrMME0rVCzMbnf3w0_fQ_G-aKtnTJNIzsTEhUCkphzHgdwsgeV7Z2zpirWNmSw2wKh2PVfhP6LY__BcHu4PJSt0Uf8UHgA7g6AdEo2VYiuanfkMsFEwoH9Ad_PkHQ</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>CUNNINGHAM, Rochelle</creator><creator>BRAZIE, Marc</creator><creator>SHENOLIKAR, Shirish</creator><creator>WEINMAN, Edward J</creator><creator>KANUMURU, Srilatha</creator><creator>XIAOFEI E</creator><creator>BISWAS, Rajat</creator><creator>FENGYING WANG</creator><creator>STEPLOCK, Deborah</creator><creator>WADE, James B</creator><creator>ANZAI, Naohiko</creator><creator>ENDOU, Hitoshi</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</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><scope>7X8</scope></search><sort><creationdate>20070501</creationdate><title>Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport</title><author>CUNNINGHAM, Rochelle ; BRAZIE, Marc ; SHENOLIKAR, Shirish ; WEINMAN, Edward J ; KANUMURU, Srilatha ; XIAOFEI E ; BISWAS, Rajat ; FENGYING WANG ; STEPLOCK, Deborah ; WADE, James B ; ANZAI, Naohiko ; ENDOU, Hitoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-c26451c3ecaabe6339d01a57f001f62787bd24d089dfa150b139eca714155f1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Kidney Tubules, Proximal - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microvilli - metabolism</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Organic Anion Transporters - metabolism</topic><topic>Phosphoproteins - genetics</topic><topic>Phosphoproteins - metabolism</topic><topic>Phosphoproteins - physiology</topic><topic>Protein Binding</topic><topic>Sodium-Hydrogen Exchangers - genetics</topic><topic>Sodium-Hydrogen Exchangers - metabolism</topic><topic>Sodium-Hydrogen Exchangers - physiology</topic><topic>Transfection</topic><topic>Uric Acid - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CUNNINGHAM, Rochelle</creatorcontrib><creatorcontrib>BRAZIE, Marc</creatorcontrib><creatorcontrib>SHENOLIKAR, Shirish</creatorcontrib><creatorcontrib>WEINMAN, Edward J</creatorcontrib><creatorcontrib>KANUMURU, Srilatha</creatorcontrib><creatorcontrib>XIAOFEI E</creatorcontrib><creatorcontrib>BISWAS, Rajat</creatorcontrib><creatorcontrib>FENGYING WANG</creatorcontrib><creatorcontrib>STEPLOCK, Deborah</creatorcontrib><creatorcontrib>WADE, James B</creatorcontrib><creatorcontrib>ANZAI, Naohiko</creatorcontrib><creatorcontrib>ENDOU, Hitoshi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CUNNINGHAM, Rochelle</au><au>BRAZIE, Marc</au><au>SHENOLIKAR, Shirish</au><au>WEINMAN, Edward J</au><au>KANUMURU, Srilatha</au><au>XIAOFEI E</au><au>BISWAS, Rajat</au><au>FENGYING WANG</au><au>STEPLOCK, Deborah</au><au>WADE, James B</au><au>ANZAI, Naohiko</au><au>ENDOU, Hitoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>18</volume><issue>5</issue><spage>1419</spage><epage>1425</epage><pages>1419-1425</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><coden>JASNEU</coden><abstract>Sodium-hydrogen exchanger regulatory factor-1-deficient (NHERF-1(-/-)) mice demonstrate increases in the urinary excretion of phosphate, calcium, and uric acid associated with interstitial deposition of calcium in the papilla of the kidney. These studies examine the role of NHERF-1 in the tubular reabsorption of uric acid and regulation of mouse urate transporter 1 (mURAT1), a newly described transporter that is responsible for the renal tubular reabsorption of uric acid. In primary cultures of mouse renal proximal tubule cells, uric acid uptake was significantly lower in NHERF-1(-/-) cells compared with wild-type cells over a large range of uric acid concentrations in the media. Western immunoblotting revealed a 56 +/- 6% decrease in the brush border membrane (BBM) expression of mURAT1 in NHERF-1(-/-) compared with wild-type control kidneys (P < 0.05). Confocal microscopy confirmed the reduced apical membrane expression of mURAT1 in NHERF-1(-/-) kidneys and demonstrated mislocalization of mURAT1 to intracellular vesicular structures. Para-aminohippurate significantly inhibited uric acid uptake in wild-type cells (41 +/- 2%) compared with NHERF-1(-/-) cells (8.2 +/- 3%). Infection of NHERF-1(-/-) cells with adenovirus-green fluorescence protein-NHERF-1 resulted in significantly higher rates of uric acid transport (15.4 +/- 1.1 pmol/microg protein per 30 min) compared with null cells that were infected with control adenovirus-green fluorescence protein (7.9 +/- 0.3) and restoration of the inhibitory effect of para-aminohippurate (% inhibition 34 +/- 4%). These findings indicate that NHERF-1 exerts a significant effect on the renal tubular reabsorption of uric acid in the mouse by modulating the BBM abundance of mURAT1 and possibly other BBM uric acid transporters.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>17409311</pmid><doi>10.1681/ASN.2006090980</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Cell Membrane - metabolism Cells, Cultured Kidney Tubules, Proximal - metabolism Male Medical sciences Membrane Proteins - metabolism Mice Mice, Inbred C57BL Mice, Knockout Microvilli - metabolism Nephrology. Urinary tract diseases Organic Anion Transporters - metabolism Phosphoproteins - genetics Phosphoproteins - metabolism Phosphoproteins - physiology Protein Binding Sodium-Hydrogen Exchangers - genetics Sodium-Hydrogen Exchangers - metabolism Sodium-Hydrogen Exchangers - physiology Transfection Uric Acid - metabolism |
| title | Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport |
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