As an important phenomenon induced by low dose radiation, radioadaptive response (RAR) is characterized by a reduction of radiobiological response in cells or tissues which have been pretreated with a low-dose radiation followed by a subsequent higher challenging dose. However, the molecular mechanism of RAR remains unclear.

To cope with this problem, the Radiobiology Division of Center of Medical Physics and technology, Hefei institutes of Physical Science, led by Prof. HAN Wei, found a critical role of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in RAR.

Nrf2/ HO-1 is an important antioxidative and protective pathway for cells. Nrf2 is sequestered in the cytoplasm by Kelch-like ECH-associated protein (Keap1) under unstimulated conditions. When stimulated, Nrf2 translocates into the nucleus, activates the antioxidant response element (ARE), and then induces the higher expression of HO-1.

In this study, researchers focused on the possible role of Nrf2/HO-1 pathway in RAR. Consistent with previous studies, priming dose of X-ray radiation (1-10 cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation levels of HO-1 were up-regulated more than two folds by a priming dose of radiation (5 cGy).

Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, mimiced 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 Nrf2, which translocated from cytoplasm to nucleus after priming dose radiation. High expression of HO-1 enhanced the antioxidant level of cells.

This work was funded by the National Natural Science Foundation of China (NSFC), the Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology, and the project was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection.

The study entitled Role of Heme Oxygenase-1 in Low Dose Radioadaptive Response has been published in Redox Biology.

Schematic of the role of Nrf2/HO-1 pathway in radioadaptive respons (Image by BAO Lingzhi)

HAN Wei

Center of Medical Physics and Technology, Hefei Institutes of Physical Science (http://english.hf.cas.cn/)

Hefei, Anhui 230031, China

Tel: +86 55165595100

Email: hanw@hfcas.ac.cn