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|Title:||Proteomic identification of alterations in metabolic enzymes and signaling proteins in hypokalemic nephropathy|
Shui Tein Chen
Genomics Research Center, Academia Sinica
National Taiwan University
Thailand National Center for Genetic Engineering and Biotechnology
Faculty of Medicine, Siriraj Hospital, Mahidol University
|Keywords:||Biochemistry, Genetics and Molecular Biology|
|Citation:||Proteomics. Vol.6, No.7 (2006), 2273-2285|
|Abstract:||Hypokalemic nephropathy caused by prolonged K+ deficiency is associated with metabolic alkalosis, polydipsia, polyuria, growth retardation, hypertension, and progressive tubulointerstitial injury. Its pathophysiology, however, remains unclear. We performed gel-based, differential proteomics analysis of kidneys from BALB/c mice fed with high-normal-K+ (HNK), low-normal-K+ (LNK), or K+-depleted diet for 8 wk (n = 6 in each group). Plasma K+ levels were 4.62 ± 0.35, 4.46 ± 0.23, and 1.51 ± 0.21 mmol/L for HNK, LNK, and KD mice, respectively (p < 0.0001; KD vs. others). With comparable amounts of food intake, the KD mice drank significantly more water than the other two groups and had polyuria. Additionally, the KD mice had growth retardation, metabolic alkalosis, markedly enlarged kidneys, renal tubular dilation, intratubular deposition of amorphous and laminated hyaline materials, and tubular atrophy. A total of 33 renal proteins were differentially expressed between the KD mice and others, whereas only eight proteins were differentially expressed between the HNK and LNK groups, as determined by quantitative intensity analysis and ANOVA with Tukey's post hoc multiple comparisons. Using MALDI-MS and/or quadrupole-TOF MS/MS, 30 altered proteins induced by K+-depletion were identified as metabolic enzymes (e.g., carbonic anhydrase II, aldose reductase, glutathione S-transferase GT41A, etc.), signaling proteins (14-3-3 ε, 14-3-3 ζ, and cofilin 1), and cytoskeletal proteins (γ-actin and tropomyosin). Some of these altered proteins, particularly metabolic enzymes and signaling proteins, have been demonstrated to be involved in metabolic alkalosis, polyuria, and renal tubular injury. Our findings may lead to a new road map for research on hypokalemic nephropathy and to better understanding of the pathophysiology of this medical disease when the functional and physiological significances of these altered proteins are defined. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.|
|Appears in Collections:||Scopus 2006-2010|
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