PMID- 20937260
OWN - NLM
STAT- MEDLINE
DCOM- 20101228
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 402
IP  - 2
DP  - 2010 Nov 12
TI  - Oleate and eicosapentaenoic acid attenuate palmitate-induced inflammation and 
      apoptosis in renal proximal tubular cell.
PG  - 265-71
LID - 10.1016/j.bbrc.2010.10.012 [doi]
AB  - 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 omega-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 PKCtheta inhibitor, prevented palmitate-induced MCP-1 expression via 
      inactivation of NFB pathway. Overexpression of dominant-negative PKCtheta also 
      inhibited palmitate-induced activation of MCP-1 promoter. Furthermore, palmitate 
      enhanced PKCtheta-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 PKCtheta 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 PKCtheta activation.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Soumura, Mariko
AU  - Soumura M
AD  - Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 
      520-2192, Japan.
FAU - Kume, Shinji
AU  - Kume S
FAU - Isshiki, Keiji
AU  - Isshiki K
FAU - Takeda, Naoko
AU  - Takeda N
FAU - Araki, Shin-ichi
AU  - Araki S
FAU - Tanaka, Yuki
AU  - Tanaka Y
FAU - Sugimoto, Toshiro
AU  - Sugimoto T
FAU - Chin-Kanasaki, Masami
AU  - Chin-Kanasaki M
FAU - Nishio, Yoshihiko
AU  - Nishio Y
FAU - Haneda, Masakazu
AU  - Haneda M
FAU - Koya, Daisuke
AU  - Koya D
FAU - Kashiwagi, Atsunori
AU  - Kashiwagi A
FAU - Maegawa, Hiroshi
AU  - Maegawa H
FAU - Uzu, Takashi
AU  - Uzu T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101016
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Isoenzymes)
RN  - 0 (NF-kappa B)
RN  - 0 (Palmitates)
RN  - 0 (Triglycerides)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - EC 2.3.1.20 (DGAT2 protein, mouse)
RN  - EC 2.3.1.20 (Diacylglycerol O-Acyltransferase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Prkcq protein, mouse)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-theta)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - *Cytoprotection
MH  - Diacylglycerol O-Acyltransferase/metabolism
MH  - Eicosapentaenoic Acid/*pharmacology
MH  - Humans
MH  - Inflammation/*chemically induced/metabolism/pathology
MH  - Isoenzymes/antagonists & inhibitors/metabolism
MH  - Kidney Tubules, Proximal/*drug effects/metabolism/pathology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Oleic Acid/*pharmacology
MH  - Palmitates/*antagonists & inhibitors/toxicity
MH  - Promoter Regions, Genetic/drug effects
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Protein Kinase C-theta
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Transcriptional Activation
MH  - Triglycerides/metabolism
EDAT- 2010/10/13 06:00
MHDA- 2010/12/29 06:00
CRDT- 2010/10/13 06:00
PHST- 2010/09/29 00:00 [received]
PHST- 2010/10/03 00:00 [accepted]
PHST- 2010/10/13 06:00 [entrez]
PHST- 2010/10/13 06:00 [pubmed]
PHST- 2010/12/29 06:00 [medline]
AID - S0006-291X(10)01863-2 [pii]
AID - 10.1016/j.bbrc.2010.10.012 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2010 Nov 12;402(2):265-71. doi: 
      10.1016/j.bbrc.2010.10.012. Epub 2010 Oct 16.