| TNF-alpha reduces the Na+/K+ ATPase activity in LLC-PK1 cells by activating caspases and JNK and inhibiting NF-kappaB. | |
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MedLine Citation:
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PMID: 20222869 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TNF-alpha has recently been implicated in diabetic nephropathy, which is usually accompanied by higher sodium retention. The kidneys play a major role in sodium homeostasis by regulating tubular sodium reabsorption, a process geared by the sodium gradient established by the Na(+)/K(+) ATPase. The aim of this work was to investigate the effect of TNF on the ATPase, and consequently its implication in kidney malfunction, using LLC-PK1 cells. The cytokine reduced the Na(+)/K(+)ATPase activity significantly. In an attempt to elucidate the signalling pathway involved, PDTC (pyrrolidinedithiocarbamate), SP600125 and FK009 respectively inhibitors of NF-kappaB, c-JNK and caspases, were added to the cells in the presence and absence of TNF, and changes in the activities of JNK and PDTC were determined. The activity of the pump was assayed by measuring the ouabain-inhibitable release of inorganic phosphate. The effect of the cytokine was abrogated completely when JNK and caspases were inhibited but was unaffected by NF-kappaB inhibition. The role of each mediator in the signalling cascade was studied further by applying different combinations of the inhibitors. TNF-alpha was found to act at 1 h by activating caspases, which in turn activate JNK; the latter exerts an inhibitory effect on NF-kappaB, a transcription factor that stimulates the Na(+)/K(+) ATPase when active. It was concluded that TNF-alpha exerts opposite effects on the Na(+)/K(+)ATPase at different times, though the effects are always mediated via cJNK, NF-kappaB and caspases. |
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Authors:
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Nancy Ramia; Sawsan Ibrahim Kreydiyyeh |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-27 |
Journal Detail:
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Title: Cell biology international Volume: 34 ISSN: 1095-8355 ISO Abbreviation: Cell Biol. Int. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-10 Completed Date: 2010-07-28 Revised Date: 2010-11-12 |
Medline Journal Info:
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Nlm Unique ID: 9307129 Medline TA: Cell Biol Int Country: England |
Other Details:
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Languages: eng Pagination: 607-13 Citation Subset: IM |
Affiliation:
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Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Animals Anthracenes / pharmacology Caspases / antagonists & inhibitors, metabolism* Cysteine Proteinase Inhibitors / pharmacology JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* LLC-PK1 Cells NF-kappa B / antagonists & inhibitors, metabolism* Pyrrolidines / pharmacology Signal Transduction Sodium-Potassium-Exchanging ATPase / metabolism* Swine Thiocarbamates / pharmacology Tumor Necrosis Factor-alpha / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Anthracenes; 0/Cysteine Proteinase Inhibitors; 0/NF-kappa B; 0/Pyrrolidines; 0/Thiocarbamates; 0/Tumor Necrosis Factor-alpha; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 25769-03-3/pyrrolidine dithiocarbamic acid; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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