Document Detail

Oleate and eicosapentaenoic acid attenuate palmitate-induced inflammation and apoptosis in renal proximal tubular cell.
MedLine Citation:
PMID:  20937260     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-16
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  402     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2010-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  265-71     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
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MeSH Terms
Apoptosis / drug effects*
Cells, Cultured
Chemokine CCL2 / genetics
Diacylglycerol O-Acyltransferase / metabolism
Eicosapentaenoic Acid / pharmacology*
Inflammation / chemically induced*,  metabolism,  pathology
Isoenzymes / antagonists & inhibitors,  metabolism
Kidney Tubules, Proximal / drug effects*,  metabolism,  pathology
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
Reg. No./Substance:
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 protein, mouse; EC O-Acyltransferase; EC 2.7.1.-/Prkcq protein, mouse; EC Proteins c-akt; EC Kinase C

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