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Int. J. Mol. Sci. 2017, 18(2), 319; doi:10.3390/ijms18020319

LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer

1
Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China
2
Departments of Urology and Pediatric Surgery, Shandong Provincial Hospital Qianfoshan Hospital, Shandong University, No. 324, Jingwu Road, Jinan 250021, China
3
Departments of Surgery, Urology, Pathology and Proteomics Laboratory, Veterans Affairs Boston Healthcare System, Boston University School of Medicine, 150 S. Huntington Ave., Boston, MA 02130, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Alan Parrish
Received: 19 October 2016 / Revised: 11 January 2017 / Accepted: 25 January 2017 / Published: 4 February 2017
(This article belongs to the Collection Advances in Proteomic Research)
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Abstract

Manganese superoxide dismutase (MNSOD) is one of the major scavengers of reactive oxygen species (ROS) in mitochondria with pivotal regulatory role in ischemic disorders, inflammation and cancer. Here we report oxidative modification of MNSOD in human renal cell carcinoma (RCC) by the shotgun method using data-dependent liquid chromatography tandem mass spectrometry (LC-MS/MS). While 5816 and 5571 proteins were identified in cancer and adjacent tissues, respectively, 208 proteins were found to be up- or down-regulated (p < 0.05). Ontological category, interaction network and Western blotting suggested a close correlation between RCC-mediated proteins and oxidoreductases such as MNSOD. Markedly, oxidative modifications of MNSOD were identified at histidine (H54 and H55), tyrosine (Y58), tryptophan (W147, W149, W205 and W210) and asparagine (N206 and N209) residues additional to methionine. These oxidative insults were located at three hotspots near the hydrophobic pocket of the manganese binding site, of which the oxidation of Y58, W147 and W149 was up-regulated around three folds and the oxidation of H54 and H55 was detected in the cancer tissues only (p < 0.05). When normalized to MNSOD expression levels, relative MNSOD enzymatic activity was decreased in cancer tissues, suggesting impairment of MNSOD enzymatic activity in kidney cancer due to modifications. Thus, LC-MS/MS analysis revealed multiple oxidative modifications of MNSOD at different amino acid residues that might mediate the regulation of the superoxide radicals, mitochondrial ROS scavenging and MNSOD activity in kidney cancer. View Full-Text
Keywords: liquid chromatography-tandem mass spectrometry; MNSOD; oxidation; ROS; quantitative proteomics liquid chromatography-tandem mass spectrometry; MNSOD; oxidation; ROS; quantitative proteomics
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Zhao, Z.; Azadzoi, K.M.; Choi, H.-P.; Jing, R.; Lu, X.; Li, C.; Wang, F.; Lu, J.; Yang, J.-H. LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer. Int. J. Mol. Sci. 2017, 18, 319.

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