Sirtuin1 and autophagy protect cells from fluoride-induced cell stress

摘要: Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during stress, including calorie restriction, endoplasmic reticulum (ER) stress oxidative stress. Previously, we reported that fluoride induces ER-stress ameloblasts responsible for enamel formation, suggesting plays role dental fluorosis. However, molecular mechanism how cells respond to fluoride-induced unclear. Here, demonstrate activates initiates protect from exposure. Fluoride treatment ameloblast-derived (LS8) significantly increased Sirt1 expression induced phosphorylation resulting augmentation activity. To exposure autophagy, characterized related genes (Atg); Atg5, Atg7 Atg8/LC3 showed both their transcript protein levels were following treatment. confirm protective toxicity, used resveratrol (RES) augment activity treated LS8 cells. RES inhibited apoptosis, decreased cytotoxicity. Rats with (0, 50, 100 125ppm) drinking water 6weeks had elevated Sirt1, maturation stage organs. Increased p-SIRT1, ATG5 ATG8/LC3 present fluoride-treated rat ameloblasts. Therefore, SIRT1/autophagy pathway may play critical as response help prevent