International journal of molecular sciences, 2017-02, Vol.18 (2), p.319-319
2017
Details
- Autor(en) / Beteiligte
- Titel
- LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer
- Ist Teil von
- International journal of molecular sciences, 2017-02, Vol.18 (2), p.319-319
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 ( < 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 (H and H ), tyrosine (Y ), tryptophan (W , W , W and W ) and asparagine (N and N ) 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 Y , W and W was up-regulated around three folds and the oxidation of H and H was detected in the cancer tissues only ( < 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms18020319Titel-ID: cdi_doaj_primary_oai_doaj_org_article_5520fc380cf244bd8f69348f25f91d9f
- Format
- –
- Schlagworte
- Amino Acid Sequence, Amino Acids - metabolism, Asparagine, Chromatography, Liquid, Cluster Analysis, Enzymatic activity, Enzyme Activation, Histidine, Humans, Hydrophobicity, Ischemia, Kidney cancer, Kidney Neoplasms - genetics, Kidney Neoplasms - metabolism, Liquid chromatography, liquid chromatography-tandem mass spectrometry, Manganese, Manganese compounds, Mass spectrometry, Mass spectroscopy, Metabolomics - methods, Methionine, Mitochondria, MNSOD, Models, Molecular, Oxidation, Oxidation-Reduction, Oxidative Stress, Protein Binding, Protein Conformation, Protein Interaction Mapping, Protein Interaction Maps, Proteins, quantitative proteomics, Reactive Oxygen Species - metabolism, Renal cell carcinoma, Residues, ROS, Scavengers, Scavenging, Signal Transduction, Superoxide dismutase, Superoxide Dismutase - chemistry, Superoxide Dismutase - metabolism, Tandem Mass Spectrometry, Tryptophan, Tyrosine, Western blotting