Preliminary Study of Mechanisms of Fluoride-Induced Suppression of Nitric Oxide Synthesis in Human Umbilical Vein Endothelial Cells
This study was aimed to determine if excessive exposure to fluoride could suppress the synthesis of nitric oxide (NO) and to detail the mechanisms involved. With the exception of the control group, human umbilical vein endothelial cells (HUVECs) were treated with sodium fluoride (NaF) (1.2 μg/mL) for 24 h, with or without a 2-h pretreatment with 100 nM insulin-like growth factor 1 (IGF-1, a PI3K/AKT agonist), or 10 μM histamine (HIS, a eNOS agonist). The levels of NO in culture fluids, as well as the expressions of eNOS, p-eNOS, PI3K, AKT, and p-AKT, were compared. The levels of NO significantly decreased in all experimental groups; however, the levels of NO were obviously higher in the NaF + HIS and NaF + IGF-1 groups, compared to the NaF group. The p-eNOS/eNOS ratios dropped clearly in NaF and NaF + HIS groups, while that in the NaF + HIS group was distinctly higher than that in the NaF group. The p-AKT/AKT ratios went down apparently in NaF and NaF + IGF-1 groups, while that in the NaF + IGF-1 group was overtly higher than that of the NaF group. Excessive exposure to fluoride inhibited the synthesis of NO. The PI3K/AKT/eNOS pathway played a crucial role in the reduced expression of NO caused by excessive fluoride exposure.
KeywordsFluoride Nitric oxide Nitric oxide synthetase PI3K/AKT
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