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Proteomes 2015, 3(2), 56-73; doi:10.3390/proteomes3020056

S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose

1
Department of Health Informatics, Rutgers School of Health Related Professions, Newark, NJ 07107, USA
2
Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
3
Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
4
Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
5
Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
6
Department of Health Informatics, Rutgers School of Health Related Professions, Newark, NJ 07107, USA
7
Department of Radiology, RUTGERS New Jersey Medical School, Newark, NJ 07103, USA
These authors contributed equally to the manuscript.
*
Authors to whom correspondence should be addressed.
Academic Editors: Michael J. Atkinson and Soile Tapio
Received: 5 March 2015 / Revised: 14 April 2015 / Accepted: 28 April 2015 / Published: 30 April 2015
(This article belongs to the Special Issue Radiation Proteomics)
View Full-Text   |   Download PDF [1418 KB, uploaded 4 May 2015]   |  

Abstract

The covalent addition of nitric oxide (NO) onto cysteine thiols, or S-nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normal S-nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined global S-nitrosylation by the “biotin switch” assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of 137Cs γ-rays. The dose of radiation was delivered to the whole body in the presence or absence of iopamidol, an iodinated contrast agent used during radiological examinations. To investigate whether similar or distinct nitrosylation patterns are induced following high-dose irradiation, mice were exposed in parallel to acute 4 Gy of 137Cs g rays. Analysis of modulated S-nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13 days after irradiation revealed radiation dose- and contrast agent-dependent changes. The major results were as follows: (i) iopamidol alone had significant effects on S-nitrosylation in brain, lung and liver; (ii) relative to the control, exposure to 0.1 Gy without iopamidol resulted in statistically-significant SNO changes in proteins that differ in molecular weight in liver, lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S-nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S-nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs; (v) mass spectrometry analyses of nitrosylated proteins in brain revealed differential modulation of SNO proteins (e.g., sodium/potassium-transporting ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high-dose irradiation; and (vi) ingenuity pathway analysis identified major signaling networks to be modulated, in particular the neuronal nitric oxide synthase signaling pathway was differentially modulated by low- and high-dose γ-irradiation. View Full-Text
Keywords: ionizing radiation; radiation sensitivity; S-nitrosylation; low- and high-dose γ ray responses; radiodiagnostic procedures; network analyses in brain ionizing radiation; radiation sensitivity; S-nitrosylation; low- and high-dose γ ray responses; radiodiagnostic procedures; network analyses in brain
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Nicolas, F.; Wu, C.; Bukhari, S.; de Toledo, S.M.; Li, H.; Shibata, M.; Azzam, E.I. S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose. Proteomes 2015, 3, 56-73.

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