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Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells
Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
School of Life Science, Xiamen University, Xiamen 361005, China
Department of Food and Environmental Sciences, Division of Food Chemistry, P.O. Box 66 (Agnes Sjöbergin katu 2), Fin-00014 University of Helsinki, Finland
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210046, China
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
* Author to whom correspondence should be addressed.
Received: 27 July 2013; in revised form: 3 September 2013 / Accepted: 4 September 2013 / Published: 30 October 2013
Abstract: Growth Arrest and DNA Damage-inducible 45 (Gadd45) and MDM2 proteins, together with p21 and p53, play important roles in cell cycle checkpoints, DNA repair, and genome integrity maintenance. Gadd45 and MDM2 were activated and transcribed instantly by UV irradiation, whereas blueberry anthocyanins (BA) decreased the gene and protein expression levels in HepG2 cells for up to 24 h, and gradually restored the UV-induced fragmented and non-fragmented DNA damage of the nucleus at a time point of 12 h. Nevertheless, UV-irradiated HepG2 cell arrests occurred mainly in the G1 phase, which indicated G1 as a checkpoint. The proteins, p21 and p53, retain cellular integrity, suppressing the oncogenic transformation by interruption of the G1 phase of the cellular cycle, giving time for repairing the damage to DNA, or apoptosis induction if the damage is too severe to be repaired, while MDM2 and Gadd45 concomitantly ensure the presence of p53 and p21. Thus, we conclude that repair, together with Gadd45 and MDM2 genes, were involved in light and dark reaction mechanisms, however, BA could interfere and assist the repair through restoration, although further studies of the complex of the gene cascades triggered and responded to in BA-assisted DNA repair are needed.
Keywords: blueberry anthocyanin (BA); cell cycle; DNA damage; UV irradiation; Gadd45; MDM2
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MDPI and ACS Style
Liu, W.; Lu, X.; He, G.; Gao, X.; Xu, M.; Zhang, J.; Li, M.; Wang, L.; Li, Z.; Wang, L.; Luo, C. Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells. Int. J. Mol. Sci. 2013, 14, 21447-21462.
Liu W, Lu X, He G, Gao X, Xu M, Zhang J, Li M, Wang L, Li Z, Wang L, Luo C. Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells. International Journal of Molecular Sciences. 2013; 14(11):21447-21462.
Liu, Wei; Lu, Xiangyi; He, Guangyang; Gao, Xiang; Xu, Maonian; Zhang, Jingkai; Li, Meiling; Wang, Lifeng; Li, Zhenjing; Wang, Likui; Luo, Cheng. 2013. "Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells." Int. J. Mol. Sci. 14, no. 11: 21447-21462.