PMID- 25147052
OWN - NLM
STAT- MEDLINE
DCOM- 20150219
LR  - 20211021
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 132
IP  - 1
DP  - 2015 Jan
TI  - Epidermal fatty acid-binding protein protects nerve growth factor-differentiated 
      PC12 cells from lipotoxic injury.
PG  - 85-98
LID - 10.1111/jnc.12934 [doi]
AB  - Epidermal fatty acid-binding protein (E-FABP/FABP5/DA11) binds and transport 
      long-chain fatty acids in the cytoplasm and may play a protecting role during 
      neuronal injury. We examined whether E-FABP protects nerve growth 
      factor-differentiated PC12 cells (NGFDPC12 cells) from lipotoxic injury observed 
      after palmitic acid (C16:0; PAM) overload. NGFDPC12 cells cultures treated with 
      PAM/bovine serum albumin at 0.3 mM/0.15 mM show PAM-induced lipotoxicity 
      (PAM-LTx) and apoptosis. The apoptosis was preceded by a cellular accumulation of 
      reactive oxygen species (ROS) and higher levels of E-FABP. Antioxidants MCI-186 
      and N-acetyl cysteine prevented E-FABP's induction in expression by PAM-LTx, 
      while tert-butyl hydroperoxide increased ROS and E-FABP expression. 
      Non-metabolized methyl ester of PAM, methyl palmitic acid (mPAM), failed to 
      increase cellular ROS, E-FABP gene expression, or trigger apoptosis. Treatment of 
      NGFDPC12 cultures with siE-FABP showed reduced E-FABP levels correlating with 
      higher accumulation of ROS and cell death after exposure to PAM. In contrast, 
      increasing E-FABP cellular levels by pre-loading the cells with recombinant 
      E-FABP diminished the PAM-induced ROS and cell death. Finally, agonists for PPARbeta 
      (GW0742) or PPARgamma (GW1929) increased E-FABP expression and enhanced the 
      resistance of NGFDPC12 cells to PAM-LTx. We conclude that E-FABP protects 
      NGFDPC12 cells from lipotoxic injury through mechanisms that involve reduction of 
      ROS. Epidermal fatty acid-binding protein (E-FABP) may protect nerve cells from 
      the damaging exposure to high levels of free fatty acids (FA). We show that 
      E-FABP can neutralize the effects of reactive oxygen species (ROS) generated by 
      the high levels of FA in the cell and protect PC12 cells from lipotoxic injuries 
      common in Type 2 diabetes neuropathy. Potentially, E-FABP gene up-regulation may 
      be mediated through the NFkB pathway and future studies are needed to further 
      evaluate this proposition.
CI  - (c) 2014 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd 
      on behalf of International Society for Neurochemistry.
FAU - Liu, Jo-Wen
AU  - Liu JW
AD  - Center for Health Disparities and Molecular Medicine, Loma Linda University 
      School of Medicine, Loma Linda, California, USA.
FAU - Montero, Manuel
AU  - Montero M
FAU - Bu, Liming
AU  - Bu L
FAU - De Leon, Marino
AU  - De Leon M
LA  - eng
GR  - P20 MD006988/MD/NIMHD NIH HHS/United States
GR  - R25 GM060507/GM/NIGMS NIH HHS/United States
GR  - 5R25GM060507/GM/NIGMS NIH HHS/United States
GR  - 5P2MD006988/MD/NIMHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140919
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Eye Proteins)
RN  - 0 (Fabp5 protein, rat)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Lipids)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Proteins)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Survival/drug effects
MH  - Eye Proteins/genetics/*physiology
MH  - Fatty Acid-Binding Proteins/genetics/*physiology
MH  - Lipids/*antagonists & inhibitors/*toxicity
MH  - Nerve Growth Factor/*pharmacology
MH  - Nerve Tissue Proteins/genetics/*physiology
MH  - PC12 Cells
MH  - Palmitic Acid/antagonists & inhibitors/toxicity
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Transfection
PMC - PMC4270845
MID - NIHMS623280
OTO - NOTNLM
OT  - FABP
OT  - PPAR
OT  - antioxidants
OT  - lipotoxicity
OT  - reactive oxygen species
EDAT- 2014/08/26 06:00
MHDA- 2015/02/20 06:00
CRDT- 2014/08/23 06:00
PHST- 2013/09/11 00:00 [received]
PHST- 2014/08/01 00:00 [revised]
PHST- 2014/08/13 00:00 [accepted]
PHST- 2014/08/23 06:00 [entrez]
PHST- 2014/08/26 06:00 [pubmed]
PHST- 2015/02/20 06:00 [medline]
AID - 10.1111/jnc.12934 [doi]
PST - ppublish
SO  - J Neurochem. 2015 Jan;132(1):85-98. doi: 10.1111/jnc.12934. Epub 2014 Sep 19.