Role of heme Oxygenase-1 in low dose Radioadaptive response

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 (1–10 cGy) 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 (5 cGy). 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.

Radioprotective agents to prevent cellular damage due to ionizing radiation

“…As skin is usually the first tissue that encounters ionizing radiation, the role of human fibroblasts have also been studied in the context of radioprotection. In a recent study, Bao et al [ 33 ] used human fibroblasts to investigate the role of hemin in the radioadaptive response. In fibroblasts, the activity of heme oxygenase 1 (HO1) was observed to increase with exposure to radiation.…”

“…In fibroblasts, the activity of heme oxygenase 1 (HO1) was observed to increase with exposure to radiation. When a competitive inhibitor of HO1 was given, this radioadaptive response was observed to decrease [ 33 ]. Conversely, when cells were treated with hemin, an inducer of HO1, radiation-related DNA damage decreased by nearly 50% [ 33 ].…”

“…When a competitive inhibitor of HO1 was given, this radioadaptive response was observed to decrease [ 33 ]. Conversely, when cells were treated with hemin, an inducer of HO1, radiation-related DNA damage decreased by nearly 50% [ 33 ]. These results suggest that upregulation of HO1 could improve cell viability after radiation exposure, making hemin a potential candidate for radioprotection [ 33 ].…”

“…Conversely, when cells were treated with hemin, an inducer of HO1, radiation-related DNA damage decreased by nearly 50% [ 33 ]. These results suggest that upregulation of HO1 could improve cell viability after radiation exposure, making hemin a potential candidate for radioprotection [ 33 ]. Another substance studied using human fibroblasts is acteoside, a known antioxidant and anti-inflammatory.…”

Flying by the seat of our pants: is low dose radiation therapy for COVID-19 an option?

“…These may contribute to its anti-inflammatory action and vascular effects. At the same time heme oxygenase-1 and other antioxidants are induced that are downstream of Nrf2 (Bao et al 2016;Rodrigues-Moreira et al 2017). Nrf2 is the master regulator of endogenous anti-oxidant, anti-stress, analgesic responses, and is also closely linked to NADPH and the pentose phosphate metabolic pathway.…”