Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage

Sossou Weyemi, Christophe E. Redon, Towqir Aziz, Rohini Choudhuri, Daisuke Maeda, Palak R. Parekh, Michael Y. Bonner, Jack L. Arbiser, William M. Bonner

Research output: Contribution to journalArticle

Abstract

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year.

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalRadiation Research
Volume183
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Fingerprint

NADPH Oxidase
oxidase
fibroblasts
Ionizing Radiation
ionizing radiation
deactivation
DNA Damage
deoxyribonucleic acid
Fibroblasts
Radiation
damage
radiation
radiation dosage
Reactive Oxygen Species
Comet Assay
Double-Stranded DNA Breaks
blood cells
oxygen
Epidemiologic Studies
Blood Cells

ASJC Scopus subject areas

  • Radiation
  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this

Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage. / Weyemi, Sossou; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; Arbiser, Jack L.; Bonner, William M.

In: Radiation Research, Vol. 183, No. 3, 01.03.2015, p. 262-270.

Research output: Contribution to journalArticle

Weyemi, S, Redon, CE, Aziz, T, Choudhuri, R, Maeda, D, Parekh, PR, Bonner, MY, Arbiser, JL & Bonner, WM 2015, 'Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage', Radiation Research, vol. 183, no. 3, pp. 262-270. https://doi.org/10.1667/RR13799.1
Weyemi, Sossou ; Redon, Christophe E. ; Aziz, Towqir ; Choudhuri, Rohini ; Maeda, Daisuke ; Parekh, Palak R. ; Bonner, Michael Y. ; Arbiser, Jack L. ; Bonner, William M. / Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage. In: Radiation Research. 2015 ; Vol. 183, No. 3. pp. 262-270.
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