Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH‐SY5Y cells
Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH‐SY5Y cells
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DOI：
10.1002/jbt.22705
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发表时间：
2021-01
影响因子：
3.6
通讯作者：
Zhi Tang;Chen-Cen Lai;Jun Luo;Yuanting Ding;Qian Chen;Z. Guan
中科院分区：
文献类型：
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作者：
Zhi Tang;Chen-Cen Lai;Jun Luo;Yuanting Ding;Qian Chen;Z. Guan
以前的研究，无论是在体内和体外都表明，高水平的氟化物会导致神经毒性。据报道芒果苷具有抗氧化、抗凋亡和抗炎特性。本研究旨在表征芒果苷保护NaF诱导的神经毒性的机制。在人神经母细胞瘤SH‐ SY 5 Y细胞中，氟化物诱导的促凋亡Bax、Caspase-3、Caspase-9和裂解型Caspase-3水平升高，以及抗凋亡Bcl-2水平降低，这些作用可通过芒果苷预处理来预防。此外，芒果苷减弱了由氟化物引起的p-JNK的增强，Nrf 2和HO-1的减少以及线粒体裂变蛋白Drp 1水平的增加。此外，氧化应激，如反应性氧簇、8-羟基-2 '-脱氧鸟苷和4-羟基壬烯醛的水平所反映的，被氟化物升高，并且这些作用再次被芒果苷改善。总之，芒果苷对氟化物诱导的神经毒性的保护作用涉及使受损的线粒体凋亡途径和动力学正常化，并通过JNK失活和Nrf 2/HO-1途径活化来减少氧化应激。
Previous studies both invivo and in vitro have revealed that high levels of fluoride cause neurotoxicity. Mangiferin has been reported to possess antioxidant, antiapoptotic, and anti‐inflammatory properties. The present study was designed to characterize the mechanisms by which mangiferin protects against NaF‐induced neurotoxicity. Increased levels of proapoptotic Bax, Caspase‐3, Caspase‐9, and cleaved‐caspase 3, as well as a decreased level of antiapoptotic Bcl‐2 induced by fluoride in human neuroblastoma SH‐SY5Y cells, these effects were prevented by pretreatment of mangiferin. In addition, mangiferin attenuated the enhancement of p‐JNK, reductions of Nrf2 and HO‐1, and increased level of the mitochondrial fission proteins Drp1 caused by fluoride. Moreover, oxidative stress, as reflected in the levels of reactive oxygen species, 8‐hydroxy‐2'‐deoxyguanosine, and 4‐hydroxynonenal, was elevated by fluoride and these effects were again ameliorated by mangiferin. In conclusion, protection by mangiferin against fluoride‐induced neurotoxicity involves normalizing the impaired mitochondrial apoptotic pathway and dynamics and reducing oxidative stress via inactivation of the JNK and activation of the Nrf2/HO‐1 pathways.