التفاصيل البيبلوغرافية
| العنوان: |
MITOCHONDRIAL FISSION INHIBITION INDUCES DEFECTIVE AUTOPHAGY AND EXCESSIVE APOPTOSIS CONTRIBUTING TO DEVELOPMENTAL FLUORIDE NEUROTOXICITY. |
| المؤلفون: |
Qian Zhao, Qiang Niu, Jing-Wen Chen, Tao Xia, Guo-Yu Zhou, Pei Li, Li-Xin Dong, Chun-Yan Xu, Zhi-Yuan Tian, Chen Luo, Lu-Ming Liu, Shun Zhang, Ai-Guo Wang |
| المصدر: |
Fluoride; Jan2019, Vol. 52 Issue 1, p86-87, 2p |
| مصطلحات موضوعية: |
NEUROTOXICOLOGY, SODIUM fluoride, CELL death, FLUORIDES, MITOCHONDRIAL membranes, DRINKING water |
| مستخلص: |
The aim of the study was to investigate how mitochondrial fusion/fission contributes to fluoride-induced developmental neurotoxicity and to illuminate the potential mechanism. SH-SY5Y cells were treated with different concentrations of sodium fluoride (NaF, 20, 40, and 60 mg/L) for 24 hr. Meanwhile, a Sprague Dawley (SD) rat model of developmental fluoride exposure from pre-pregnancy until 2 months after delivery was constructed and four groups (n=10) were set up: control group, three NaF-treated groups (NaF was administered at 10, 50, and 100 mg/L via dissolving with tap water). Mdivi-1 and Fis1 overexpression were employed to further explore the role of mitochondrial fission in fluoride-induced mitochondrial dysfunction and cell death. Wortmannin and ACDEVD- CHO were used to test the influence of autophagy and apoptosis on the ultimate cellular viability, respectively. The mitochondrial morphology and function, representative mitochondrial fusion/fission, autophagy and apoptosis proteins, apoptotic rate, and cellular viability were detected. We found that NaF induced dysregulated mitochondrial fission/fusion which was manifested by inhibited fission and accelerated fusion, and was accompanied by mitochondrial heterogeneity and dysfunction such as mitochondrial membrane potential loss and mitochondrial superoxide overproduction in the SH-SY5Y cells. Mechanically, suppressing mitochondrial fission with Mdivi-1 exacerbated the NaF-induced mitochondrial injury and the resultant neuronal death was via excessive apoptosis and promoted autophagy. However, targeting promoting mitochondrial fission by Fis1 overexpression alleviated the NaF-induced detrimental outcomes by inhibiting apoptosis and enhancing autophagy. Furthermore, the promoted autophagy and excessive apoptosis after mitochondrial fission interference were validated to be beneficial and harmful for cellular survival, respectively. Mitochondrial fission reduction and fusion accession occurred consistently in the hippocampus in the NaFexposed offspring rats with cognitive deficits and neuron damage, accompanied by defective autophagy and excessive apoptosis. Taken together, our results suggest that mitochondrial fission inhibition and the subsequent mitochondrial dysfunction trigger defective autophagy and excessive apoptosis contributing to developmental fluoride neurotoxicity. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
