Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule
Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na + excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport an...
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| Veröffentlicht in: | Kidney & blood pressure research 2012-01, Vol.36 (1), p.320-334 |
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| creator | Queiroz-Leite, Gabriella D. Crajoinas, Renato O. Neri, Elida A. Bezerra, Camila N. A. Girardi, Adriana C. C. Rebouças, Nancy Amaral Malnic, Gerhard |
| description | Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na + excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO 3 - reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH 4 Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na + reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension. |
| doi_str_mv | 10.1159/000343390 |
| format | Article |
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A. ; Girardi, Adriana C. C. ; Rebouças, Nancy Amaral ; Malnic, Gerhard</creator><creatorcontrib>Queiroz-Leite, Gabriella D. ; Crajoinas, Renato O. ; Neri, Elida A. ; Bezerra, Camila N. A. ; Girardi, Adriana C. C. ; Rebouças, Nancy Amaral ; Malnic, Gerhard</creatorcontrib><description>Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na + excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO 3 - reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH 4 Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na + reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension.</description><identifier>ISSN: 1420-4096</identifier><identifier>EISSN: 1423-0143</identifier><identifier>DOI: 10.1159/000343390</identifier><identifier>PMID: 23235337</identifier><identifier>CODEN: RPBIEL</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Animals ; Cell Line ; Cells, Cultured ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Fructokinases - metabolism ; Fructose - pharmacology ; Glucose Transporter Type 2 - metabolism ; Glucose Transporter Type 5 - metabolism ; Kidney Tubules, Proximal - cytology ; Kidney Tubules, Proximal - drug effects ; Kidney Tubules, Proximal - metabolism ; LLC-PK1 Cells ; Male ; Models, Animal ; Original Paper ; Rats ; Rats, Wistar ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Sodium-Hydrogen Exchanger 3 ; Sodium-Hydrogen Exchangers - metabolism ; Swine</subject><ispartof>Kidney & blood pressure research, 2012-01, Vol.36 (1), p.320-334</ispartof><rights>2012 S. Karger AG, Basel</rights><rights>Copyright © 2012 S. Karger AG, Basel.</rights><rights>Copyright (c) 2013 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-af694ea899b08f2e3f1a179574f434377a1f3de60c578b3b479404e57260e7393</citedby><cites>FETCH-LOGICAL-c435t-af694ea899b08f2e3f1a179574f434377a1f3de60c578b3b479404e57260e7393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23235337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Queiroz-Leite, Gabriella D.</creatorcontrib><creatorcontrib>Crajoinas, Renato O.</creatorcontrib><creatorcontrib>Neri, Elida A.</creatorcontrib><creatorcontrib>Bezerra, Camila N. A.</creatorcontrib><creatorcontrib>Girardi, Adriana C. C.</creatorcontrib><creatorcontrib>Rebouças, Nancy Amaral</creatorcontrib><creatorcontrib>Malnic, Gerhard</creatorcontrib><title>Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule</title><title>Kidney & blood pressure research</title><addtitle>Kidney Blood Press Res</addtitle><description>Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na + excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO 3 - reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH 4 Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na + reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension.</description><subject>Animals</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Fructokinases - metabolism</subject><subject>Fructose - pharmacology</subject><subject>Glucose Transporter Type 2 - metabolism</subject><subject>Glucose Transporter Type 5 - metabolism</subject><subject>Kidney Tubules, Proximal - cytology</subject><subject>Kidney Tubules, Proximal - drug effects</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>LLC-PK1 Cells</subject><subject>Male</subject><subject>Models, Animal</subject><subject>Original Paper</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Sodium-Hydrogen Exchanger 3</subject><subject>Sodium-Hydrogen Exchangers - metabolism</subject><subject>Swine</subject><issn>1420-4096</issn><issn>1423-0143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0D1PwzAQBmALgWgpDOwIRWKBIWD7nDgeq6qliAqQKHPkpBeUkjTFH4j8e1JaOjCddXp8unsJOWf0lrFI3VFKQQAoekD6THAIKRNw-PumoaAq7pETa5cdiyjlx6THgUMEIPtkNDE-d43FYJh7h1UbvLqy9pV2aIOn6Ri6viu_StcG5Sp4LBcrbIMX03yXta6Cuc98hafkqNCVxbNdHZC3yXg-moaz5_uH0XAW5gIiF-oiVgJ1olRGk4IjFEwzqSIpCtGtL6VmBSwwpnkkkwwyIZWgAiPJY4oSFAzI9Xbu2jSfHq1L69LmWFV6hY23KQMmBeU82dCrf3TZeLPqtku7aCLBEh5v1M1W5aax1mCRrk13l2lTRtNNsuk-2c5e7ib6rMbFXv5F2YGLLfjQ5h3NHuz-_wCO2nir</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>Queiroz-Leite, Gabriella D.</creator><creator>Crajoinas, Renato O.</creator><creator>Neri, Elida A.</creator><creator>Bezerra, Camila N. 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A.</au><au>Girardi, Adriana C. C.</au><au>Rebouças, Nancy Amaral</au><au>Malnic, Gerhard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule</atitle><jtitle>Kidney & blood pressure research</jtitle><addtitle>Kidney Blood Press Res</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>36</volume><issue>1</issue><spage>320</spage><epage>334</epage><pages>320-334</pages><issn>1420-4096</issn><eissn>1423-0143</eissn><coden>RPBIEL</coden><abstract>Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na + excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO 3 - reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH 4 Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na + reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>23235337</pmid><doi>10.1159/000343390</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Line Cells, Cultured Cyclic AMP - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Fructokinases - metabolism Fructose - pharmacology Glucose Transporter Type 2 - metabolism Glucose Transporter Type 5 - metabolism Kidney Tubules, Proximal - cytology Kidney Tubules, Proximal - drug effects Kidney Tubules, Proximal - metabolism LLC-PK1 Cells Male Models, Animal Original Paper Rats Rats, Wistar Signal Transduction - drug effects Signal Transduction - physiology Sodium-Hydrogen Exchanger 3 Sodium-Hydrogen Exchangers - metabolism Swine |
| title | Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule |
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