title: 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.
abstract: The covalent addition of nitric oxide (NO•) onto cysteine thiols, orS-nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normalS-nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined globalS-nitrosylation by the "biotin switch" assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of137Cs 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 of137Cs γ rays. Analysis of modulatedS-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 onS-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 inS-nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease inS-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.
authors: Department of Health Informatics, Rutgers School of Health Related Professions, Newark, NJ 07107, USA; nicolafa@shrp.rutgers.edu.
authors: Fadia
authors: F
authors: Nicolas
authors: Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; wuchanggong1@yahoo.com.
authors: Changgong
authors: C
authors: Wu
authors: Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; salwa.bukhari@gmail.com.
authors: Salwa
authors: S
authors: Bukhari
authors: Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; detolesm@njms.rutgers.edu.
authors: Sonia M
authors: SM
authors: de Toledo
authors: Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; liho2@njms.rutgers.edu.
authors: Hong
authors: H
authors: Li
authors: Department of Health Informatics, Rutgers School of Health Related Professions, Newark, NJ 07107, USA.
authors: Masayuki
authors: M
authors: Shibata
authors: Department of Radiology, RUTGERS New Jersey Medical School, Newark, NJ 07103, USA.
authors: Edouard I
authors: EI
authors: Azzam
keywords: S-nitrosylation; ionizing radiation; low- and high-dose γ ray responses; network analyses in brain; radiation sensitivity; radiodiagnostic procedures