Oxidized low-density lipoprotein induced mouse hippocampal HT-22 cell damage via promoting the shift from autophagy to apoptosis
Oxidized low-density lipoprotein induced mouse hippocampal HT-22 cell damage via promoting the shift from autophagy to apoptosis
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DOI：
10.1111/cns.12680
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发表时间：
2017-04-01
影响因子：
5.5
通讯作者：
Liao, Duan-Fang
中科院分区：
文献类型：
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作者：
Gu, Hong-Feng;Li, Hai-Zhe;Liao, Duan-Fang
虽然脑内氧化低密度脂蛋白（ox-LDL）可诱导神经元死亡，但其损伤作用的机制仍不清楚。鉴于细胞的最终结局取决于自噬和凋亡之间的平衡，本研究旨在探讨ox-LDL是否通过自噬损伤和凋亡增强引起HT-22神经细胞损伤。结果100 g/mL ox-LDL可促进TH-22细胞凋亡，表现为细胞凋亡率和Bax蛋白表达增加，Bcl-2蛋白表达降低，细胞超微结构受损，细胞凋亡率降低，Bcl-2蛋白表达降低，Bax蛋白表达降低，细胞凋亡率升高，Bcl-2蛋白表达降低，细胞凋亡率降低，Bax蛋白表达降低，细胞凋亡率降低，Bcl-2蛋白表达降低，细胞凋亡率降低，Bcl-2蛋白表达降低，细胞凋亡率降低，Bcl-2蛋白表达降低，细胞凋亡率降低。而且如降低的LC 3-II水平和增加的p62水平所示，也损害了自噬。重要的是，所有这些影响ox-LDL显着加剧了共同治疗与氯喹（自噬通量的抑制剂）。与此相反，与雷帕霉素（自噬诱导剂）的共治疗显着逆转ox-LDL的这些影响。ConclusionsTaken在一起，我们的研究结果表明，ox-LDL诱导的转变，从自噬到凋亡有助于HT-22细胞损伤。
AimsAlthough oxidized low-density lipoprotein (ox-LDL) in the brain induces neuronal death, the mechanism underlying the damage effects remains largely unknown. Given that the ultimate outcome of a cell is depended on the balance between autophagy and apoptosis, this study was performed to explore whether ox-LDL induced HT-22 neuronal cell damage via autophagy impairment and apoptosis enhancement.MethodsFlow cytometry and transmission electron microscopy (TEM) were used to evaluate changes in cell apoptosis and autophagy, respectively. The protein expression of LC3-II, p62, Bcl-2, and Bax in HT-22 cells was measured by Western bolt analysis.ResultsOur study confirmed that 100g/mL of ox-LDL not only promoted TH-22 cell apoptosis, characterized by elevated cell apoptosis rate and Bax protein expression, decreased Bcl-2 protein expression, and damaged cellular ultrastructures, but also impaired autophagy as indicated by the decreased LC3-II levels and the increased p62 levels. Importantly, all of these effects of ox-LDL were significantly aggravated by cotreatment with chloroquine (an inhibitor of autophagy flux). In contrast, cotreatment with rapamycin (an inducer of autophagy) remarkably reversed these effects of ox-LDL.ConclusionsTaken together, our results indicated that ox-LDL-induced shift from autophagy to apoptosis contributes to HT-22 cell damage.