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Antioxidants 2015, 4(1), 68-81; doi:10.3390/antiox4010068

Modulation of Radiation Response by the Tetrahydrobiopterin Pathway

1
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Biomed II, Room 441A-2, 4301 West Markham #522-10, Little Rock, AR 72205, USA
2
Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA
3
Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA
4
Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC 20057, USA
5
Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Nikolai Gorbunov
Received: 18 November 2014 / Revised: 7 January 2015 / Accepted: 13 January 2015 / Published: 22 January 2015
(This article belongs to the Special Issue Redox Stress and Redox Homeostatic Response to Trauma and Injury)
View Full-Text   |   Download PDF [192 KB, uploaded 22 January 2015]   |  

Abstract

Ionizing radiation (IR) is an integral component of our lives due to highly prevalent sources such as medical, environmental, and/or accidental. Thus, understanding of the mechanisms by which radiation toxicity develops is crucial to address acute and chronic health problems that occur following IR exposure. Immediate formation of IR-induced free radicals as well as their persistent effects on metabolism through subsequent alterations in redox mediated inter- and intracellular processes are globally accepted as significant contributors to early and late effects of IR exposure. This includes but is not limited to cytotoxicity, genomic instability, fibrosis and inflammation. Damage to the critical biomolecules leading to detrimental long-term alterations in metabolic redox homeostasis following IR exposure has been the focus of various independent investigations over last several decades. The growth of the “omics” technologies during the past decade has enabled integration of “data from traditional radiobiology research”, with data from metabolomics studies. This review will focus on the role of tetrahydrobiopterin (BH4), an understudied redox-sensitive metabolite, plays in the pathogenesis of post-irradiation normal tissue injury as well as how the metabolomic readout of BH4 metabolism fits in the overall picture of disrupted oxidative metabolism following IR exposure. View Full-Text
Keywords: ionizing radiation; metabolomics; oxidative stress; tetrahydrobiopterin ionizing radiation; metabolomics; oxidative stress; tetrahydrobiopterin
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

Pathak, R.; Cheema, A.K.; Boca, S.M.; Krager, K.J.; Hauer-Jensen, M.; Aykin-Burns, N. Modulation of Radiation Response by the Tetrahydrobiopterin Pathway. Antioxidants 2015, 4, 68-81.

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