Role of heme Oxygenase-1 in low dose Radioadaptive response

Lingzhi Bao; Jie Ma; Guodong Chen; Jue Hou; Tom K Hei; K N Yu; Wei Han

doi:10.1016/j.redox.2016.03.002

Role of heme Oxygenase-1 in low dose Radioadaptive response

Redox Biol. 2016 Aug:8:333-40. doi: 10.1016/j.redox.2016.03.002. Epub 2016 Mar 3.

Authors

Lingzhi Bao¹, Jie Ma², Guodong Chen¹, Jue Hou¹, Tom K Hei³, K N Yu⁴, Wei Han⁵

Affiliations

¹ Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
² Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China; University of Science and Technology of China, Hefei, Anhui, China.
³ Center for Radiological Research, Columbia University, New York, NY, USA.
⁴ Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong; Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
⁵ Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, Jiangsu, China. Electronic address: [email protected].

Abstract

Radioadaptive response (RAR) is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1) in RAR. Consistent with previous studies, priming dose of X-ray radiation (1-10cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5cGy). Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells.

Keywords: Heme Oxygenase 1; Hemin; Nrf2; Radioadaptive response; Reactive oxidative species; Znpp.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antioxidants / metabolism*
Cell Line
Cell Nucleolus / metabolism
Cell Nucleolus / radiation effects
Cytoplasm / radiation effects
Dose-Response Relationship, Radiation
Fibroblasts / metabolism*
Fibroblasts / radiation effects
Gene Expression Regulation / radiation effects
Heme Oxygenase-1 / antagonists & inhibitors
Heme Oxygenase-1 / genetics*
Hemin / genetics
Hemin / metabolism
Humans
NF-E2-Related Factor 2 / genetics*
NF-E2-Related Factor 2 / metabolism
Protoporphyrins / genetics
Protoporphyrins / metabolism
RNA, Small Interfering / genetics
X-Rays

Substances

Antioxidants
NF-E2-Related Factor 2
NFE2L2 protein, human
Protoporphyrins
RNA, Small Interfering
zinc protoporphyrin
Hemin
Heme Oxygenase-1