| Oleate and eicosapentaenoic acid attenuate palmitate-induced inflammation and apoptosis in renal proximal tubular cell. | |
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MedLine Citation:
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PMID: 20937260 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Free fatty acid (FFA)-bound albumin, which is filtrated through the glomeruli and reabsorbed into proximal tubular cells, is one of the crucial mediators of tubular damage in proteinuric kidney disease. In this study, we examined the role of each kind of FFA on renal tubular damage in vitro and tried to identify its molecular mechanism. In cultured proximal tubular cells, a saturated fatty acid, palmiate, increased the expression of monocyte chemoattractant protein-1 (MCP-1), but this effect was abrogated by co-incubation of monounsaturated fatty acid, oleate, or ω-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA). Palmitate led to intracellular accumulation of diacylglycerol (DAG) and subsequent activation of protein kinase C protein family. Among the several PKC inhibitors, rottlerin, a PKCθ inhibitor, prevented palmitate-induced MCP-1 expression via inactivation of NFB pathway. Overexpression of dominant-negative PKCθ also inhibited palmitate-induced activation of MCP-1 promoter. Furthermore, palmitate enhanced PKCθ-dependent mitochondrial apoptosis, which was also prevented by co-incubation with oleate or EPA through restoration of pro-survival Akt pathway. Moreover, oleate and EPA inhibited palmitate-induced PKCθ activation through the conversion of intracellular DAG to triglyceride with the restoration of diacylglycerol acyltransferase 2 expression. These results suggest that oleate and EPA have protective effects against the palmitate-induced renal tubular cell damage by inhibiting PKCθ activation. |
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Authors:
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Mariko Soumura; Shinji Kume; Keiji Isshiki; Naoko Takeda; Shin-ichi Araki; Yuki Tanaka; Toshiro Sugimoto; Masami Chin-Kanasaki; Yoshihiko Nishio; Masakazu Haneda; Daisuke Koya; Atsunori Kashiwagi; Hiroshi Maegawa; Takashi Uzu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-16 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 402 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-15 Completed Date: 2010-12-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 265-71 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Cells, Cultured Chemokine CCL2 / genetics Cytoprotection* Diacylglycerol O-Acyltransferase / metabolism Eicosapentaenoic Acid / pharmacology* Humans Inflammation / chemically induced*, metabolism, pathology Isoenzymes / antagonists & inhibitors, metabolism Kidney Tubules, Proximal / drug effects*, metabolism, pathology Mice NF-kappa B / metabolism Oleic Acid / pharmacology* Palmitates / antagonists & inhibitors*, toxicity Promoter Regions, Genetic / drug effects Protein Kinase C / antagonists & inhibitors, metabolism Proto-Oncogene Proteins c-akt / metabolism Transcriptional Activation Triglycerides / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Ccl2 protein, mouse; 0/Chemokine CCL2; 0/Isoenzymes; 0/NF-kappa B; 0/Palmitates; 0/Triglycerides; 112-80-1/Oleic Acid; 1553-41-9/Eicosapentaenoic Acid; EC 2.3.1.20/DGAT2 protein, mouse; EC 2.3.1.20/Diacylglycerol O-Acyltransferase; EC 2.7.1.-/Prkcq protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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