Journal of Cellular Biochemistry

A Phenolic Acid Phenethyl Urea Derivative Protects Against Irradiation-Induced Osteoblast Damage by Modulating Intracellular Redox State

Authors

  • Kyoung A. Kim,

    1. Department of Oral and Maxillofacial Radiology and Research Institute of Clinical Medicine, Chonbuk National University, Jeonju, South Korea
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  • Sung-Ho Kook,

    1. Department of Orthodontics, and Institute of Oral Biosciences, Chonbuk National University, Jeonju, South Korea
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  • Ji-Hye Song,

    1. Department of Orthodontics, and Institute of Oral Biosciences, Chonbuk National University, Jeonju, South Korea
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  • Jeong-Chae Lee

    Corresponding author
    1. Department of Orthodontics, and Institute of Oral Biosciences, Chonbuk National University, Jeonju, South Korea
    2. Research Center of Bioactive Materials, Chonbuk National University, Jeonju, South Korea
    • Correspondence to: Prof. Jeong-Chae Lee, Department of Orthodontics and Institute of Oral Biosciences (BK21 program), Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756, South Korea.

      E-mail: leejc88@jbnu.ac.kr

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  • Kyoung A. Kim and Sung-Ho Kook contributed equally to this work.

ABSTRACT

Because irradiation may cause osteoradionecrosis, antioxidant supplementation is often used to suppress irradiation-mediated injury. This study examined whether a synthetic phenethyl urea compound, (E)-1-(3,4-dihydroxyphenethyl)-3-(3,4-dihydroxystyryl)urea (DPDS-U), prevents irradiation-mediated cellular damage in MC3T3-E1 osteoblastic cells. A relatively high dose of irradiation (>4 Gy) decreased cell viability and proliferation and induced DNA damage and cell cycle arrest at the G2/M phase with the attendant increase of cyclin B1. Irradiation with 8 Gy induced intracellular reactive oxygen species (ROS) production and lipid peroxidation, and reduced glutathione content and superoxide dismutase activity in the cells. These events were significantly suppressed by treatment with 200 µM DPDS-U or 5 mM N-acetyl cysteine (NAC). DPDS-U or irradiation alone significantly increased heme oxygenase-1 (HO-1) expression and nuclear factor E2 p45-related factor-2 (Nrf2) nuclear translocation. Interestingly, pretreatment with DPDS-U facilitated irradiation-induced activation of the Nrf2/HO-1 pathway. The potential of DPDS-U to mediate HO-1 induction and protect against irradiation-mediated cellular damage was almost completely attenuated by transient transfection with Nrf2-specific siRNA or treatment with a pharmacological HO-1 inhibitor, zinc protoporphyrin IX. Additional experiments revealed that DPDS-U induced a radioprotective mechanism that differs from that induced by NAC through activation of Nrf2/HO-1 signaling. Collectively, our data suggest that DPDS-U-induced radioprotection is due to its dual function as an antioxidant to remove directly excessive intracellular ROS and as a prooxidant to stimulate intracellular redox-sensitive survival signal. J. Cell. Biochem. 115: 1877–1887, 2014. © 2014 Wiley Periodicals, Inc.

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