SIRT has deacetylated regulation on numerous nonhistone
SIRT1 has deacetylated regulation on numerous nonhistone protein substrates [Atgs, Foxo1, Foxo3, PGC-1α, NF-kB, E2F1 and p53] (Conrad et al., 2016) to play a key role in protecting against cell stress. Therefore, the role of SIRT1 in fluorine-induced oxidative stress was explored. The results revealed that group pretreated with SRT1720 significantly reduced the intracellular ROS level compared with NaF group; whereas group pretreated with Ex-527 presented a more significant increase of ROS level. It suggested that SIRT1 activation attenuated the increase of intracellular ROS level.
Here, the role of SIRT1 in fluorine-induced apoptosis and dexamethasone acetate mg was also investigated. The Annexin V-FITC/PI dual staining results showed that apoptosis rate was attenuated after pretreatment with SRT1720 and exacerbated after pretreatment with Ex-527 when compared with group treated with NaF alone. In addition, pretreatment of SRT1720 caused an inhibition at the S-phase arrest. Furthermore, the protein expression of Ac-p53, p21 and Caspase-3 presented a significant reduction with pretreatment of SRT1720, and p53 protein expression remained unchanged， when compared with treatment with NaF alone. Acetylation increases p53 protein stability, binding to promoters, and association with signaling proteins. Ac-p53 is indispensable for cell cycle checkpoint responses to DNA damage. Additionally, Ac-p53 develops its regulation effect on cell cycle arrest via cyclin-dependent kinase inhibitor 1A/p21 (CDKN1A/p21) and modulates apoptosis (Bao et al., 2016). SIRT1 deacetylates p53 at Lys379 to inhibit p53-dependent apoptosis (Suzuki et al., 2018). The results of the study demonstrate that SIRT1-mediated p53 deacetylation is critical to alleviating mitochondrial-mediated intrinsic cell apoptosis and growth inhibition during fluoride toxicity. The regulation of p53 acetylation by fluoride and SIRT1 in the current study was shown in Fig. 10.
Introduction The skeleton is renewed by 10% annually. Osteoporosis is a bone metabolic disease characterized by low bone mass and decreased bone strength, and it is a common disorder among older, postmenopausal, or estrogen-deficient women. Osteoporosis poses a great burden on the elderly. It is well accepted that the imbalance in bone resorption and bone formation may be critically involved in the pathophysiology of osteoporosis. The combination of increased bone resorption with decreased bone formation result in significant reductions in bone mass, contributing to net bone loss or osteoporosis. Osteoblasts are crucial to bone formation. Therefore, promoting the proliferation and differentiation of osteoblast precursor cells may be a promising target for developing osteoporosis treatment strategies. It is generally accepted that excess reactive oxygen species (ROS) can induce multiple disorders, including bone loss, while moderate levels of ROS exhibit a physiological intracellular signaling role, leading to cell proliferation and differentiation.7, 8, 9 Recently, researchers have focused on the roles of NAD(P)H oxidase-derived ROS in regulating bone formation and resorption. However, results from different group are inconsistent. Loss of functional NOX2 reportedly protects against alcohol-induced bone resorption in female mice.10, 11 However, a host of evidences suggest that NAD(P)H oxidases may play a protective role in promoting bone formation. It has been demonstrated that NOX2 knockout mice exhibit spontaneous bone destruction and aging-dependent development of arthritis. Bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation was shown to depend on NOX4-derived ROS. Another study corroborated the view that ROS-dependent signaling plays a role in osteoblast differentiation. However, the effects of NAD(P)H oxidases-derived ROS on bone formation remain controversial. We hypothesized that the absolute levels of ROS production determine their effects, with moderately elevated ROS having beneficial effects on bone formation.