PMID- 19634143
OWN - NLM
STAT- MEDLINE
DCOM- 20091231
LR  - 20131121
IS  - 1615-9861 (Electronic)
IS  - 1615-9853 (Linking)
VI  - 9
IP  - 18
DP  - 2009 Sep
TI  - Quantitative proteomic profiling identifies new renal targets of 
      copper(II)-selective chelation in the reversal of diabetic nephropathy in rats.
PG  - 4309-20
LID - 10.1002/pmic.200900285 [doi]
AB  - This study aimed to identify new diabetic nephropathy (DN)-related proteins and 
      renal targets of the copper(II)-selective chelator, triethylenetetramine (TETA) 
      in streptozotocin-diabetic rats. We used the recently developed iTRAQ technology 
      to compare renal protein profiles among non-diabetic, diabetic, and TETA-treated 
      diabetic rats. In diabetic kidneys, tubulointerstitial nephritis antigen (TINag), 
      voltage-dependent anion-selective channel (VDAC) 1, and VDAC2 were up-regulated 
      in parallel with alterations in expression of proteins with functions in 
      oxidative stress and oxidative phosphorylation (OxPhos) pathways. By contrast, 
      mitochondrial HSP 60, Cu/Zn-superoxide dismutase, glutathione S-transferase 
      alpha3 and aquaporin-1 were down-regulated in diabetic kidneys. Following TETA 
      treatment, levels of D-amino acid oxidase-1, epoxide hydrolase-1, aquaporin-1, 
      and a number of mitochondrial proteins were normalized, with concomitant 
      amelioration of albuminuria. Changes in levels of TINag, collagen VIalpha1, 
      actinin 4alpha, apoptosis-inducing factor 1, cytochrome C, histone H3, VDAC1, and 
      aquaporin-1 were confirmed by Western blotting or immunohistochemistry. Changes 
      in expression of proteins related to tubulointerstitial function, podocyte 
      structure, and mitochondrial apoptosis are implicated in the mechanism of DN and 
      their reversal by TETA. These findings are consistent with the hypothesis that 
      this new experimental therapy may be useful for treatment of DN.
FAU - Gong, Deming
AU  - Gong D
AD  - School of Biological Sciences, University of Auckland, Auckland, New Zealand.
FAU - Chen, Xiuyin
AU  - Chen X
FAU - Middleditch, Martin
AU  - Middleditch M
FAU - Huang, Liangdong
AU  - Huang L
FAU - Vazhoor Amarsingh, Greeshma
AU  - Vazhoor Amarsingh G
FAU - Reddy, Shiva
AU  - Reddy S
FAU - Lu, Jun
AU  - Lu J
FAU - Zhang, Shaoping
AU  - Zhang S
FAU - Ruggiero, Katya
AU  - Ruggiero K
FAU - Phillips, Anthony R J
AU  - Phillips AR
FAU - Cooper, Garth J S
AU  - Cooper GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Proteomics
JT  - Proteomics
JID - 101092707
RN  - 0 (Cations)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chelating Agents)
RN  - 0 (Collagen Type VI)
RN  - 789U1901C5 (Copper)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - SJ76Y07H5F (Trientine)
SB  - IM
MH  - Animals
MH  - Cations/metabolism
MH  - Cell Adhesion Molecules/metabolism
MH  - Chelating Agents/*pharmacology
MH  - Collagen Type VI/metabolism
MH  - Copper/*metabolism
MH  - Diabetes Mellitus, Experimental/drug therapy/*metabolism/urine
MH  - Diabetic Nephropathies/drug therapy/*metabolism/urine
MH  - Down-Regulation
MH  - Glutathione Peroxidase/metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Nephritis, Interstitial/metabolism
MH  - Proteomics/*methods
MH  - Rats
MH  - Rats, Wistar
MH  - Superoxide Dismutase/metabolism
MH  - Trientine/*pharmacology
MH  - Up-Regulation
EDAT- 2009/07/28 09:00
MHDA- 2010/01/01 06:00
CRDT- 2009/07/28 09:00
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2010/01/01 06:00 [medline]
AID - 10.1002/pmic.200900285 [doi]
PST - ppublish
SO  - Proteomics. 2009 Sep;9(18):4309-20. doi: 10.1002/pmic.200900285.