PMID- 23088929
OWN - NLM
STAT- MEDLINE
DCOM- 20130704
LR  - 20160518
IS  - 1876-7737 (Electronic)
IS  - 1874-3919 (Linking)
VI  - 78
DP  - 2013 Jan 14
TI  - An iTRAQ-based mitoproteomics approach for profiling the nephrotoxicity 
      mechanisms of ochratoxin A in HEK 293 cells.
PG  - 398-415
LID - S1874-3919(12)00705-1 [pii]
LID - 10.1016/j.jprot.2012.10.010 [doi]
AB  - Nephrotoxicity is the most prominent of ochratoxin A (OTA) among the diverse 
      range of toxicological effects. Previous work indicated that reactive oxygen 
      species (ROS) play an important role in the pathogenesis of a variety of renal 
      diseases, and its major endogenous source is mitochondria. No research has used 
      global protein expression profiling to investigate potential toxicity mechanisms 
      of OTA at the mitochondria level. An iTRAQ-based mitoproteomics approach was used 
      to explore possible toxicity mechanisms of OTA and potential protective 
      mechanisms of N-acetyl-L-cysteine (NAC) using the mitochondria of Human Embryonic 
      Kidney 293 (HEK 293) cells. Our results showed that OTA induced a decrease in 
      DeltaPsim, and an increase in ROS and cell death. We identified a total of 1973 
      nonredundant proteins, among which 1398 proteins (70.86%) were overlapped. There 
      were 66 significantly different proteins expressed in response to OTA, which were 
      mainly involved in the perturbation of the mitochondrial electron transport chain 
      (mETC), inhibition of protein synthesis, and induction of stress response and 
      cell death. In addition, NAC could almost completely reverse the adverse effects 
      of OTA at the protein level. Finally, a hypothetical model of OTA-induced 
      mitochondria damage is proposed to provide a framework for the toxicity mechanism 
      of OTA.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Shen, Xiao Li
AU  - Shen XL
AD  - Laboratory of food safety and molecular biology, College of Food Science and 
      Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
FAU - Zhang, Yu
AU  - Zhang Y
FAU - Xu, Wentao
AU  - Xu W
FAU - Liang, Rui
AU  - Liang R
FAU - Zheng, Juanjuan
AU  - Zheng J
FAU - Luo, YunBo
AU  - Luo Y
FAU - Wang, Yan
AU  - Wang Y
FAU - Huang, Kunlun
AU  - Huang K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121023
PL  - Netherlands
TA  - J Proteomics
JT  - Journal of proteomics
JID - 101475056
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Electron Transport Chain Complex Proteins)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Ochratoxins)
RN  - 1779SX6LUY (ochratoxin A)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Calcium Channel Blockers/*adverse effects/pharmacology
MH  - Electron Transport Chain Complex Proteins/metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Kidney Diseases/chemically induced/*metabolism/pathology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/*metabolism/pathology
MH  - Mitochondrial Proteins/*biosynthesis
MH  - *Models, Biological
MH  - Ochratoxins/*adverse effects/pharmacology
EDAT- 2012/10/24 06:00
MHDA- 2013/07/05 06:00
CRDT- 2012/10/24 06:00
PHST- 2012/07/26 00:00 [received]
PHST- 2012/09/28 00:00 [revised]
PHST- 2012/10/11 00:00 [accepted]
PHST- 2012/10/24 06:00 [entrez]
PHST- 2012/10/24 06:00 [pubmed]
PHST- 2013/07/05 06:00 [medline]
AID - S1874-3919(12)00705-1 [pii]
AID - 10.1016/j.jprot.2012.10.010 [doi]
PST - ppublish
SO  - J Proteomics. 2013 Jan 14;78:398-415. doi: 10.1016/j.jprot.2012.10.010. Epub 2012 
      Oct 23.