Cathepsin L is involved in 6-hydroxydopamine induced apoptosis of SH-SY5Y neuroblastoma cells

Cathepsin L is involved in 6-hydroxydopamine induced apoptosis of SH-SY5Y neuroblastoma cells
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组织蛋白酶L参与6-羟基多巴胺诱导的SH-SY5Y神经母细胞瘤细胞凋亡

DOI:
10.1016/j.brainres.2011.02.092
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发表时间:
2011-04
期刊:
影响因子:
2.9
通讯作者:
Liang, Zhongqin
Liang, Zhongqin
中科院分区:
医学3区
文献类型:
--
作者:
Xiang, Bei;Fei, Xifeng;Zhuang, Wenzhuo;Fang, Yun;Qin, Zhenghong;Liang, Zhongqin

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我们的前期研究报道了组织蛋白酶L可能参与了帕金森病(PD)大鼠模型多巴胺能神经元的死亡。本研究检测了PD细胞模型中溶酶体组织蛋白酶L表达的变化。在人神经母细胞瘤SH-SY 5 Y细胞中,用6-羟基多巴胺处理引起细胞质中组织蛋白酶L免疫反应性的增加和组织蛋白酶L活性形式的产生增加。用组织蛋白酶L的不可逆抑制剂Z-FY(t-Bu)-DMK评价组织蛋白酶L对6-OHDA诱导的NF-κB活化和SH-SY 5 Y神经母细胞瘤细胞死亡的贡献。Z-FY(t-Bu)-DMK可部分阻断6-OHDA诱导的IκB-α降解、NF-κB p65核转位、p53和p53 A表达。此外,Z-FY(t-Bu)- DMK调节Bcl-2家族水平,并抑制caspase-3活化。这些数据表明,组织蛋白酶L可能参与6-OHDA诱导的细胞凋亡和帕金森病神经变性。
Our previous study reported that cathepsin L may contribute to the death of dopaminergic neurons in rodent model of Parkinson's disease (PD). In this study we detected the changes in the expression of lysosomal cathepsin L in cellular models of PD. In human neuroblastoma SH-SY5Y cells, treatment with 6-hydroxydopamine caused an increase in cathepsin L immunoreactivity in the cytoplasm and an increased production of the active form of cathepsin L. The contribution of cathepsin L to 6-OHDA-induced NF-κB activation and death of SH-SY5Y neuroblastoma cells were evaluated with an irreversible inhibitor of cathepsin L, Z-FY(t-Bu)-DMK. 6-OHDA-induced IκB-α degradation, NF-κB p65 nuclear translocation, p53 and PUMA expression were partially blocked by Z-FY(t-Bu)-DMK. In addition, Z-FY(t-Bu)- DMK modulated the Bcl-2 family levels, and suppressed caspase-3 activation. These data indicate that cathepsin L may be involved in 6-OHDA-induced apoptosis and Parkinsonian neurodegeneration.
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