Role of JNK in hypertonic activation of Cl(-)-dependent Na(+)/H(+) exchange in Xenopus oocytes.
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 approximately 3mM. 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.
Goss
G G
GG
Department of Biological Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
Jiang
L
L
Vandorpe
D H
DH
Kieller
D
D
Chernova
M N
MN
Robertson
M
M
Alper
S L
SL
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions / Q000737:chemistry; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D009994:Osmolar Concentration; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D012979:Sodium Radioisotopes / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014982:Xenopus laevis
D000838:Anions; D000873:Anthracenes; D002614:Chelating Agents; D002712:Chlorides; D004232:Diuretics; D004791:Enzyme Inhibitors; D006982:Hypertonic Solutions; D011993:Recombinant Fusion Proteins; D012979:Sodium Radioisotopes; D017923:Sodium-Hydrogen Exchangers; C432165:pyrazolanthrone; D004533:Egtazic Acid; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium