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  • Actinonin clinical br Acknowledgements This work was support

    2019-09-11


    Acknowledgements This work was supported by National Natural Science Foundation of China (No. 81400241).
    Introduction Fluoride, as a member of the halogen group of elements, naturally existed in water, soil, animals, and plants around the world (Singh et al., 2018), and it is present in trace amounts in all mineralized tissues such as dentin, enamel and bone. It is documented that fluoride could enhance the stability of mineralized tissues and materials since it weakens inclusive mineral phase in tissues and materials (Tressaud and Haufe, 2008). Therefore, fluoride is used extensively to prevent dental caries; however, excessive ingestion may cause side effects of fluoride exposure and result in serious health hazards. Excessive fluoride intake may damage a variety of organs and tissues such as skeletal, nervous, digestive, respiratory, genitourinary and endocrine systems (Del Piero, 2013). Literatures show that fluoride affects diverse signaling pathways associated with proliferation and apoptosis, such as mitogen-activated protein kinase (MAPK), p53, activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB) pathways (Iwatsuki and Matsuoka, 2016; Zhang et al., 2007, 2008). It is also reported that fluoride has an adverse effect on the Actinonin clinical but it brings out various impacts which rest in different cell types (Ribeiro et al., 2017). Research data in hepatocytes cultured in vitro indicate that fluoride increased cell number at S phase and decreased cells at G2/M or G0/G1phase (Liu et al., 2018). p53 is activated in response to several malignancy-associated stress signals, giving rise to the inhibition of tumor cell growth (Garritano et al., 2013). Several responses can be elicited by p53, including cell cycle arrest, senescence, differentiation and apoptosis. The p53 protein is controlled by many different forms of post-translational modifications, including ubiquitylation, phosphorylation, acetylation, sumoylation, methylation, and neddylation (Lee and Gu, 2010; Muller and Vousden, 2013; Solomon et al., 2017). Acetylation is of vital importance to regulation of p53. It increases the protein stability of p53, binding to low affinity promoters, association with other proteins, antiviral activities, and is required for its checkpoint responses to DNA damage and activated oncogenes (Munoz-Fontela et al., 2011; Reed and Quelle, 2014; Zhang et al., 2015; Zhao et al., 2015). As an example, p300-mediated acetylation of p53 in human cancer cell lines has been implicated for p21 promoter transactivation and cell cycle arrest (Iyer et al., 2004; Li et al., 2006; Shi et al., 2016). Previous studies reported that p53/p21-mediated cell cycle leads to genetic mutations in mice (Kuroda et al., 2015). SIRT1 is a representative member of Sirtuins, which is a family of highly conserved NAD+-dependent class III histone deacetylases. SIRT1 deacetylates plentiful nonhistone protein substrates [Atgs, Foxo1, Foxo3, PGC-1α, NF-kB, E2F1 and p53] (Conrad et al., 2016; Gu et al., 2016; Tu et al., 2018) to play a key role in resistance of cell stress. Many studies back it up that SIRT1 is a vital negative regulator of p53. SIRT1 (Luo et al., 2001; Wang et al., 2018) may deacetylate p53 and intensively inhibit p53-dependent transcription, thereby inverting p53-mediated cell growth arrest and apoptosis in response to DNA damage or oxidative stress. However, SIRT1-p53 relationship is somewhat complicated. Therefore, aim of this study was to investigate the impact of SIRT1 and p53 in fluoride-induced apoptosis and cell cycle arrest in MC3T3-E1 cells.
    Materials and methods
    Results
    Discussion Fluoride is an important industrial chemical and mostly used in power-generating stations, welding operations, in the manufacture of fluoridated dental preparations and the fluoridation of drinking water (Choubisa and Choubisa, 2016). Fluorosis not only injury teeth and the skeletal system but also damage the structure and functions of the non-skeletal systems such as liver, kidney and ovary (Dharmaratne, 2015; Yin et al., 2015; Zhou et al., 2015). The present study was undertaken to investigate the effect of different concentrations of sodium fluoride on oxidative stress, Actinonin clinical mitochondria-dependent apoptosis pathway, cell cycle as well as acetylation status of p53 and explore the acetylation regulation by SIRT1.