Quantitative proteomic profiling identifies new renal targets of copper(II)-selective chelation in the reversal of diabetic nephropathy in rats

Deming Gong, Xiuyin Chen, Martin Middleditch, Liangdong Huang, Greeshma Vazhoor Amarsingh, Shiva Reddy, Jun Lu, Shaoping Zhang, Katya Ruggiero, Anthony R J Phillips, Garth Cooper

Research output: Contribution to journalArticlepeer-review

Abstract

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 α3 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 VIα1, actinin 4α, 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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Original languageEnglish
Pages (from-to)4309-4320
Number of pages11
JournalProteomics
Volume9
Issue number18
DOIs
Publication statusPublished - Sept 2009

Keywords

  • Animal proteomics
  • Diabetic nephropathy
  • iTRAQ™
  • Kidney
  • Triethylenetetramine

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