Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes

1  Department of Biological Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E9, 2  Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston; and Departments of 3  Medicine and 4  Cell Biology, Harvard Medical School, Boston, Massachusetts 02215 In the course of...

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Veröffentlicht in:American Journal of Physiology: Cell Physiology 2001-12, Vol.281 (6), p.C1978-C1990
Hauptverfasser: Goss, Greg G, Jiang, Lianwei, Vandorpe, David H, Kieller, Dawn, Chernova, Marina N, Robertson, Marilyn, Alper, Seth L
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container_end_page C1990
container_issue 6
container_start_page C1978
container_title American Journal of Physiology: Cell Physiology
container_volume 281
creator Goss, Greg G
Jiang, Lianwei
Vandorpe, David H
Kieller, Dawn
Chernova, Marina N
Robertson, Marilyn
Alper, Seth L
description 1  Department of Biological Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E9, 2  Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston; and Departments of 3  Medicine and 4  Cell Biology, Harvard Medical School, Boston, Massachusetts 02215 In the course of studying the hypertonicity-activated ion transporters in Xenopus oocytes, we found that activation of endogenous oocyte Na + /H + exchange activity (xoNHE) by hypertonic shrinkage required Cl , with an EC 50 for bath [Cl ] of ~3 mM. This requirement for chloride was not supported by several nonhalide anions and was not shared by xoNHE activated by acid loading. Hypertonicity-activated xoNHE exhibited an unusual rank order of inhibitory potency among amiloride derivatives and was blocked by Cl transport inhibitors. Chelation of intracellular Ca 2+ by injection of EGTA blocked hypertonic activation of xoNHE, although many inhibitors of Ca 2+ -related signaling pathways were without inhibitory effect. Hypertonicity activated oocyte extracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors of neither ERK1/2 nor p38 prevented hypertonic activation of xoNHE. However, hypertonicity also stimulated a Cl -dependent increase in c-Jun NH 2 -terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE but not activation by acid loading. We conclude that hypertonic activation of Na + /H + exchange in Xenopus oocytes requires Cl and is mediated by activation of JNK. Na + /H + exchange; c-Jun NH 2 -terminal kinase; extracellular signal-regulated kinase; p38; transport; SP600125; U-0126
doi_str_mv 10.1152/ajpcell.2001.281.6.c1978
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This requirement for chloride was not supported by several nonhalide anions and was not shared by xoNHE activated by acid loading. Hypertonicity-activated xoNHE exhibited an unusual rank order of inhibitory potency among amiloride derivatives and was blocked by Cl transport inhibitors. Chelation of intracellular Ca 2+ by injection of EGTA blocked hypertonic activation of xoNHE, although many inhibitors of Ca 2+ -related signaling pathways were without inhibitory effect. Hypertonicity activated oocyte extracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors of neither ERK1/2 nor p38 prevented hypertonic activation of xoNHE. However, hypertonicity also stimulated a Cl -dependent increase in c-Jun NH 2 -terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE but not activation by acid loading. We conclude that hypertonic activation of Na + /H + exchange in Xenopus oocytes requires Cl and is mediated by activation of JNK. 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This requirement for chloride was not supported by several nonhalide anions and was not shared by xoNHE activated by acid loading. Hypertonicity-activated xoNHE exhibited an unusual rank order of inhibitory potency among amiloride derivatives and was blocked by Cl transport inhibitors. Chelation of intracellular Ca 2+ by injection of EGTA blocked hypertonic activation of xoNHE, although many inhibitors of Ca 2+ -related signaling pathways were without inhibitory effect. Hypertonicity activated oocyte extracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors of neither ERK1/2 nor p38 prevented hypertonic activation of xoNHE. However, hypertonicity also stimulated a Cl -dependent increase in c-Jun NH 2 -terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE but not activation by acid loading. We conclude that hypertonic activation of Na + /H + exchange in Xenopus oocytes requires Cl and is mediated by activation of JNK. 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Jiang, Lianwei ; Vandorpe, David H ; Kieller, Dawn ; Chernova, Marina N ; Robertson, Marilyn ; Alper, Seth L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-b8df37cd0f874e41c7a0a75f2e013daf13eadd9237898e7620780305cc3fb7813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amiloride - analogs &amp; derivatives</topic><topic>Amiloride - pharmacology</topic><topic>Animals</topic><topic>Anions - pharmacology</topic><topic>Anthracenes - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Chelating Agents - pharmacology</topic><topic>Chlorides - metabolism</topic><topic>Diuretics - pharmacology</topic><topic>Egtazic Acid - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Hydrogen - metabolism</topic><topic>Hydrogen-Ion Concentration</topic><topic>Hypertonic Solutions - chemistry</topic><topic>JNK Mitogen-Activated Protein Kinases</topic><topic>Mitogen-Activated Protein Kinases - antagonists &amp; inhibitors</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Oocytes - physiology</topic><topic>Osmolar Concentration</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Sodium - metabolism</topic><topic>Sodium Radioisotopes - metabolism</topic><topic>Sodium-Hydrogen Exchangers - metabolism</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goss, Greg G</creatorcontrib><creatorcontrib>Jiang, Lianwei</creatorcontrib><creatorcontrib>Vandorpe, David H</creatorcontrib><creatorcontrib>Kieller, Dawn</creatorcontrib><creatorcontrib>Chernova, Marina N</creatorcontrib><creatorcontrib>Robertson, Marilyn</creatorcontrib><creatorcontrib>Alper, Seth L</creatorcontrib><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>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goss, Greg G</au><au>Jiang, Lianwei</au><au>Vandorpe, David H</au><au>Kieller, Dawn</au><au>Chernova, Marina N</au><au>Robertson, Marilyn</au><au>Alper, Seth L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>281</volume><issue>6</issue><spage>C1978</spage><epage>C1990</epage><pages>C1978-C1990</pages><issn>0363-6143</issn><eissn>1522-1563</eissn><abstract>1  Department of Biological Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E9, 2  Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston; and Departments of 3  Medicine and 4  Cell Biology, Harvard Medical School, Boston, Massachusetts 02215 In the course of studying the hypertonicity-activated ion transporters in Xenopus oocytes, we found that activation of endogenous oocyte Na + /H + exchange activity (xoNHE) by hypertonic shrinkage required Cl , with an EC 50 for bath [Cl ] of ~3 mM. This requirement for chloride was not supported by several nonhalide anions and was not shared by xoNHE activated by acid loading. Hypertonicity-activated xoNHE exhibited an unusual rank order of inhibitory potency among amiloride derivatives and was blocked by Cl transport inhibitors. Chelation of intracellular Ca 2+ by injection of EGTA blocked hypertonic activation of xoNHE, although many inhibitors of Ca 2+ -related signaling pathways were without inhibitory effect. Hypertonicity activated oocyte extracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors of neither ERK1/2 nor p38 prevented hypertonic activation of xoNHE. However, hypertonicity also stimulated a Cl -dependent increase in c-Jun NH 2 -terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE but not activation by acid loading. We conclude that hypertonic activation of Na + /H + exchange in Xenopus oocytes requires Cl and is mediated by activation of JNK. Na + /H + exchange; c-Jun NH 2 -terminal kinase; extracellular signal-regulated kinase; p38; transport; SP600125; U-0126</abstract><cop>United States</cop><pmid>11698257</pmid><doi>10.1152/ajpcell.2001.281.6.c1978</doi></addata></record>
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subjects Amiloride - analogs & derivatives
Amiloride - pharmacology
Animals
Anions - pharmacology
Anthracenes - pharmacology
Calcium - metabolism
Chelating Agents - pharmacology
Chlorides - metabolism
Diuretics - pharmacology
Egtazic Acid - pharmacology
Enzyme Inhibitors - pharmacology
Female
Hydrogen - metabolism
Hydrogen-Ion Concentration
Hypertonic Solutions - chemistry
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Oocytes - physiology
Osmolar Concentration
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Sodium - metabolism
Sodium Radioisotopes - metabolism
Sodium-Hydrogen Exchangers - metabolism
Xenopus laevis
title Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes
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