Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
Department of Rehabilitation, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5143-5150. doi: 10.3892/mmr.2017.7303. Epub 2017 Aug 21.
The aim of the present study was to examine the protective effects and mechanism of sika deer (Cervus nippon Temminck) velvet antler polypeptides (VAPs) against MPP+ exposure in the SH‑SY5Y human neuroblastoma cell line. MPP+ cytotoxicity and the protective effects of VAPs on the SH‑SY5Y cells were determined using an MTT assay. Cell apoptosis and mitochondrial membrane potential were detected using Hoechst 33342 and Rhodamine123 staining, respectively. Endoplasmic reticulum (ER) stress‑related reactive oxygen species (ROS) production in the SH‑SY5Y cells was detected using 2',7'‑dichlorodihydrofluorescein diacetate fluorescent probes. The expression levels of proteins, including caspase‑12, glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and phosphorylated c‑Jun N‑terminal kinase (p‑JNK) were detected using western blot analysis. The results showed that the half inhibitory concentration of MPP+ at 72 h was 120.9 µmol/l, and that 62.5, 125, and 250 µg/ml concentrations of VAPs protected the SH‑SY5Y cells under MPP+ exposure. When exposed to 120.9 µmol/l MPP+, changes in cell nucleus morphology, mitochondrial membrane potential and intracellular ROS were observed. VAPs at concentrations of 62.5, 125, 250 µg/ml reduced this damage. Western blot analysis showed that protein expression levels of caspase‑12, GRP78 and p‑JNK were upregulated in the SH‑SY5Y cells exposed to 120.9 µmol/l MPP+ for 72 h. In addition, 62.5, 125, and 250 µg/ml VAPs downregulated the expression levels of caspase‑12 and p‑JNK in a concentration‑ dependent manner, particularly the p‑JNK pathway. The effects of VAPs on GRP78 and CHOP were weak. In conclusion, MPP+‑induced SH‑SY5Y cell death may be linked to ER stress. VAPs prevented MPP+‑induced SH‑SY5Y cell death by affecting the p‑JNK pathway and caspase‑12‑mediated apoptosis. These findings assist in understanding the mechanism underlying the protective effect of VAPs on neurons.
本研究旨在探讨梅花鹿(Cervus nippon Temminck)鹿茸多肽(VAP)对 MPP+暴露诱导的 SH-SY5Y 人神经母细胞瘤细胞损伤的保护作用及其机制。采用 MTT 比色法检测 MPP+的细胞毒性以及 VAP 对 SH-SY5Y 细胞的保护作用。采用 Hoechst 33342 和 Rhodamine123 染色分别检测细胞凋亡和线粒体膜电位。采用 2',7'-二氯二氢荧光素二乙酸荧光探针检测 SH-SY5Y 细胞内质网(ER)应激相关活性氧(ROS)的产生。采用 Western blot 分析检测半胱氨酸天冬氨酸蛋白酶-12(caspase-12)、葡萄糖调节蛋白 78(GRP78)、CCAAT/增强子结合蛋白同源蛋白(CHOP)和磷酸化 c-Jun N-末端激酶(p-JNK)蛋白的表达水平。结果显示,72 h 时 MPP+的半抑制浓度为 120.9 μmol/L,62.5、125 和 250 μg/ml VAP 浓度可在 MPP+暴露下保护 SH-SY5Y 细胞。当暴露于 120.9 μmol/L MPP+时,观察到细胞核形态、线粒体膜电位和细胞内 ROS 的变化。62.5、125 和 250 μg/ml VAP 减轻了这种损伤。Western blot 分析结果显示,暴露于 120.9 μmol/L MPP+ 72 h 后,SH-SY5Y 细胞 caspase-12、GRP78 和 p-JNK 的蛋白表达水平上调。此外,62.5、125 和 250 μg/ml VAP 呈浓度依赖性地下调 caspase-12 和 p-JNK 的表达水平,尤其是 p-JNK 通路。VAP 对 GRP78 和 CHOP 的影响较弱。综上所述,MPP+诱导的 SH-SY5Y 细胞死亡可能与 ER 应激有关。VAP 通过影响 p-JNK 通路和 caspase-12 介导的细胞凋亡来防止 MPP+诱导的 SH-SY5Y 细胞死亡。这些发现有助于理解 VAP 对神经元保护作用的机制。