Fluoride induces apoptosis via inhibiting SIRT1 activity to activate mitochondrial p53 pathway in human neuroblastoma SH-SY5Y cells

Fluoride induces apoptosis via mitochondrial p53 signaling pathway by inhibiting SIRT1 deacetylase activity. SIRT1 could deacetylate p53 at lysine 382. Fluoride inhibited the deacetylase activity of SIRT1, therefore upregulated acetyl p53 (K382) and increased nuclear translocation and transcriptional activity of p53. The pro-apoptotic proteins PUMA and Bax are downstream targets of p53. Oligomerization of Bax in mitochondrial outer membrane led to mitochondrial outer membrane permeabilization, cyto c release from mitochondria to cytoplasm, caspase-3 and PARP cleavage, and ultimate apoptosis.221