Protective Roles of Gadd45 and MDM2 in Blueberry Anthocyanins Mediated DNA Repair of Fragmented and Non-Fragmented DNA Damage in UV-Irradiated HepG2 Cells

被引:20
作者
Liu, Wei [1 ]
Lu, Xiangyi [1 ]
He, Guangyang [2 ]
Gao, Xiang [1 ]
Xu, Maonian [3 ]
Zhang, Jingkai [1 ]
Li, Meiling [1 ]
Wang, Lifeng [4 ]
Li, Zhenjing [1 ]
Wang, Likui [5 ]
Luo, Cheng [1 ]
机构
[1] Tianjin Univ Sci & Technol, Sch Food Engn & Biotechnol, Key Lab Food Nutr & Safety, Minist Educ, Tianjin 300457, Peoples R China
[2] Xiamen Univ, Sch Life Sci, Xiamen 361005, Peoples R China
[3] Univ Helsinki, Div Food Chem, Dept Food & Environm Sci, FIN-00014 Helsinki, Finland
[4] Nanjing Univ Finance & Econ, Coll Food Sci & Engn, Nanjing 210046, Jiangsu, Peoples R China
[5] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
关键词
blueberry anthocyanin (BA); cell cycle; DNA damage; UV irradiation; Gadd45; MDM2; CYCLE CHECKPOINTS; OXIDATIVE STRESS; P53; PHOSPHORYLATION; IDENTIFICATION; PROGRESSION; EXTRACTION; APOPTOSIS; CANCER; ATM;
D O I
10.3390/ijms141121447
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:21447 / 21462
页数:16
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