Wei Min, Duan Dongmei, Liu Yujie, Wang Zhigang, Li Zhongli
Department of Orthopaedics, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Mol Med Rep. 2014 Jun;9(6):2309-15. doi: 10.3892/mmr.2014.2079. Epub 2014 Mar 28.
Fluoride is an essential trace element for all mammalian species; however, excess fluoride intake is known to be toxic to cells in animals and humans. The toxicity of fluoride is mainly exerted via induction of apoptosis. Autophagy is induced by numerous cytotoxic stimuli; however, it is often unclear whether, under specific conditions, autophagy has a pro‑survival or a pro‑apoptotic role. To answer this critical question, the present study assessed autophagy and apoptosis simultaneously in single cells. It was demonstrated that fluoride was able to inhibit cell proliferation and induce apoptosis and autophagy, whereas autophagy appeared to be protective. Further analysis revealed that MAPK/JNK‑dependent autophagy may be protective in fluoride‑induced apoptosis. It is anticipated that the presented single‑cell approach may be a powerful tool for gaining a quantitative understanding of the complex regulation of autophagy, its effect on cell fate and its association with other cellular pathways.
氟化物是所有哺乳动物物种必需的微量元素；然而，已知过量摄入氟化物对动物和人类细胞有毒性。氟化物的毒性主要通过诱导细胞凋亡来发挥作用。自噬由多种细胞毒性刺激诱导；然而，在特定条件下，自噬是具有促生存作用还是促凋亡作用往往并不明确。为了回答这个关键问题，本研究在单细胞中同时评估了自噬和凋亡。结果表明，氟化物能够抑制细胞增殖并诱导凋亡和自噬，而自噬似乎具有保护作用。进一步分析显示，丝裂原活化蛋白激酶/应激活化蛋白激酶（MAPK/JNK）依赖的自噬可能对氟化物诱导的凋亡具有保护作用。预计所提出的单细胞方法可能是一种强大的工具，有助于定量了解自噬的复杂调控、其对细胞命运的影响以及与其他细胞途径的关联。
