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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container_title | American Journal of Physiology: Cell Physiology |
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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 |
format | Article |
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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</description><identifier>ISSN: 0363-6143</identifier><identifier>EISSN: 1522-1563</identifier><identifier>DOI: 10.1152/ajpcell.2001.281.6.c1978</identifier><identifier>PMID: 11698257</identifier><language>eng</language><publisher>United States</publisher><subject>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</subject><ispartof>American Journal of Physiology: Cell Physiology, 2001-12, Vol.281 (6), p.C1978-C1990</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-b8df37cd0f874e41c7a0a75f2e013daf13eadd9237898e7620780305cc3fb7813</citedby><cites>FETCH-LOGICAL-c467t-b8df37cd0f874e41c7a0a75f2e013daf13eadd9237898e7620780305cc3fb7813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11698257$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes</title><title>American Journal of Physiology: Cell Physiology</title><addtitle>Am J Physiol Cell Physiol</addtitle><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</description><subject>Amiloride - analogs & derivatives</subject><subject>Amiloride - pharmacology</subject><subject>Animals</subject><subject>Anions - pharmacology</subject><subject>Anthracenes - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Chelating Agents - pharmacology</subject><subject>Chlorides - metabolism</subject><subject>Diuretics - pharmacology</subject><subject>Egtazic Acid - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Hydrogen - metabolism</subject><subject>Hydrogen-Ion Concentration</subject><subject>Hypertonic Solutions - chemistry</subject><subject>JNK Mitogen-Activated Protein Kinases</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Oocytes - physiology</subject><subject>Osmolar Concentration</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Sodium - metabolism</subject><subject>Sodium Radioisotopes - metabolism</subject><subject>Sodium-Hydrogen Exchangers - metabolism</subject><subject>Xenopus laevis</subject><issn>0363-6143</issn><issn>1522-1563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtP4zAQxy20CLqFr4B84oIS_EhshxuqeOyCQEIgcbNcZ9IYpXE2ToB8exK1LFw4zeH_mJkfQpiSmNKUnZqXxkJVxYwQGjNFYxFbmkm1g2ajzCKaCv4LzQgXPBI04fvodwgvhJCEiWwP7VMqMsVSOUPPD74C7Av89-4GuxqXQwNt52tnsbGdezWd8_WkL6ooyqGBOoe6w3fm5PT6BMO7LU29gin5DLVv-oC9t0MH4QDtFqYKcLidc_R0efG4uI5u76_-LM5vI5sI2UVLlRdc2pwUSiaQUCsNMTItGBDKc1NQDibPM8alyhRIwYhUhJPUWl4spaJ8jo43vU3r__UQOr12YYJjavB90JIxwYRKR6PaGG3rQ2ih0E3r1qYdNCV6oqq3VPVEVY9UtdCLieoYPdru6JdryL-CW4yj4WxjKN2qfHMt6KYcgvOVXw36sq-qR3jvPvu_Netm_H6O4p_D_2_6ds4Hy-qaWg</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>Goss, Greg G</creator><creator>Jiang, Lianwei</creator><creator>Vandorpe, David H</creator><creator>Kieller, Dawn</creator><creator>Chernova, Marina N</creator><creator>Robertson, Marilyn</creator><creator>Alper, Seth L</creator><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>20011201</creationdate><title>Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes</title><author>Goss, Greg G ; 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 & 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 & 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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identifier | ISSN: 0363-6143 |
ispartof | American Journal of Physiology: Cell Physiology, 2001-12, Vol.281 (6), p.C1978-C1990 |
issn | 0363-6143 1522-1563 |
language | eng |
recordid | cdi_pubmed_primary_11698257 |
source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
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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