PMID- 21664458
OWN - NLM
STAT- MEDLINE
DCOM- 20111202
LR  - 20110815
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 51
IP  - 6
DP  - 2011 Sep 15
TI  - SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal 
      tubular cells.
PG  - 1258-67
LID - 10.1016/j.freeradbiomed.2011.05.028 [doi]
AB  - Free fatty acid (FFA)-mediated renal lipotoxicity is associated with the 
      progression of tubulointerstitial inflammation in proteinuric kidney disease. 
      SIRT3 is an antiaging molecule regulated by calorie restriction and 
      mitochondria-localized NAD(+)-dependent deacetylase. In this study, we 
      investigated whether SIRT3 reversed renal lipotoxicity-mediated ROS and 
      inflammation. In the kidney of the FFA-bound BSA-overloaded mouse, which is a 
      well-established experimental model of FFA-associated tubulointerstitial 
      inflammation, mRNA expression of SIRT3 was significantly decreased and negatively 
      correlated with mRNA expression of an inflammatory cytokine, monocyte 
      chemoattractant protein-1 (MCP-1). In cultured proximal tubular (mProx) cells, 
      the saturated FFA palmitate stimulated ROS accumulation and expression of MCP-1. 
      These effects were ameliorated by retrovirus-mediated overexpression of SIRT3, 
      whereas they were exacerbated by either overexpression of a dominant-negative 
      form of SIRT3(N87A) lacking deacetylase activity or knockdown of SIRT3 by siRNA 
      transfection. Furthermore, we showed that SIRT3 positively regulated both 
      mitochondrial oxidative capacity and antioxidant gene expression, thereby 
      reducing ROS accumulation in mProx cells, which suggests a mechanism that 
      underlies SIRT3-mediated reversal of palmitate-induced inflammation. In 
      conclusion, these results highlight a new role for SIRT3 in 
      lipotoxicity/ROS-related inflammation, reveal a new molecular mechanism 
      underlying calorie restriction-mediated antioxidant and anti-inflammatory 
      effects, and could aid in the design of new therapies for the prevention of 
      tubulointerstitial lesions in proteinuric kidney disease.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Koyama, Tetsuro
AU  - Koyama T
AD  - Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 
      520-2192, Japan.
FAU - Kume, Shinji
AU  - Kume S
FAU - Koya, Daisuke
AU  - Koya D
FAU - Araki, Shin-ichi
AU  - Araki S
FAU - Isshiki, Keiji
AU  - Isshiki K
FAU - Chin-Kanasaki, Masami
AU  - Chin-Kanasaki M
FAU - Sugimoto, Toshiro
AU  - Sugimoto T
FAU - Haneda, Masakazu
AU  - Haneda M
FAU - Sugaya, Takeshi
AU  - Sugaya T
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 - 20110530
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Palmitates)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sirt3 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 3)
SB  - IM
MH  - Animals
MH  - Caloric Restriction
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Inflammation
MH  - Kidney Tubules, Proximal/immunology/*metabolism/pathology
MH  - Mice
MH  - Mutation/genetics
MH  - Nephritis, Interstitial/diet therapy/immunology/*metabolism/pathology
MH  - Oxidative Stress/genetics
MH  - Palmitates/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Reactive Oxygen Species/metabolism
MH  - Sirtuin 3/genetics/*metabolism
MH  - Transgenes/genetics
EDAT- 2011/06/15 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/06/14 06:00
PHST- 2010/11/15 00:00 [received]
PHST- 2011/03/31 00:00 [revised]
PHST- 2011/05/23 00:00 [accepted]
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - S0891-5849(11)00344-3 [pii]
AID - 10.1016/j.freeradbiomed.2011.05.028 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2011 Sep 15;51(6):1258-67. doi: 
      10.1016/j.freeradbiomed.2011.05.028. Epub 2011 May 30.