SMND-309 promotes neuron survival through the activation of the PI3K/Akt/CREB-signalling pathway

被引:29
作者
Wang, Youlei [1 ]
Zhang, Jinjin [1 ]
Han, Meng [2 ]
Liu, Bo [1 ]
Gao, Yulin [1 ]
Ma, Peng [1 ]
Zhang, Songzi [3 ]
Zheng, Qingyin [1 ,4 ]
Song, Xiaodong [1 ]
机构
[1] Binzhou Med Univ, Sch Special Educ, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China
[2] Zibo Occupat Dis Hosp, Zibo, Peoples R China
[3] Taishan Med Coll, Sch Pharm, Tai An, Shandong, Peoples R China
[4] Case Western Reserve Univ, Dept Otolaryngol HNS, Cleveland, OH 44106 USA
基金
中国国家自然科学基金;
关键词
Apoptosis; differentiated SH-SY5Y cells; oxygen-glucose deprivation/reperfusion; SALVIANOLIC ACID-B; OSTEOBLASTIC MC3T3-E1 CELLS; SH-SY5Y NEUROBLASTOMA-CELLS; ISCHEMIA-REPERFUSION INJURY; PI3K/AKT SIGNALING PATHWAY; ELEMENT-BINDING PROTEIN; RAT CORTICAL-NEURONS; CEREBRAL-ISCHEMIA; NEUROTROPHIC FACTOR; MITOCHONDRIAL-FUNCTION;
D O I
10.3109/13880209.2015.1137951
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Context In clinical practice, the promotion of neuron survival is necessary to recover neurological functions after the onset of stroke. Objective This study aimed to investigate the post-ischaemic neuroprotective effect of SMND-309, a novel metabolite of salvianolic acid, on differentiated SH-SY5Y cells. Materials and methods SH-SY5Y cells were differentiated by pre-treating with 5 mu M all-transretinoic acid for 6 d. The differentiated SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD) for 2 h and reperfusion (R) for 24 h to induce OGD/R injury. After OGD injury, differentiated SH-SY5Y cells were treated with or without SMND-309 (5, 10, 20 mu M) for another 24 h. Cell viability was detected through Cell counting kit-8 assay and lactate dehydrogenase leakage assay. Apoptosis was evaluated through flow cytometry, caspase-3 activity assay. Changes in protein levels were assessed through Western blot. Results SMND-309 ameliorated the degree of injury in the differentiated SH-SY5Y cells by increasing cell viabilities (5 mu M, 65.4% +/- 4.1%; 10 mu M, 69.8% +/- 3.7%; 20 mu M, 75.3% +/- 5.1%) and by reducing LDH activity (20 mu M, 2.5 fold) upon OGD/R stimulation. Annexin V-fluorescein isothiocyanate/propidium iodide staining results suggested that apoptotic rate of differentiated SH-SY5Y cells decreased from 43.8% induced by OGD/R injury to 19.2% when the cells were treated with 20 mM SMND-309. SMND-309 significantly increased the Bcl-2 level of the injured differentiated SH-SY5Y cells but decreased the caspase-3 activity of these cells by 1.6-fold. In contrast, SMND- 309 did not affect the Bax level of these cells. SMND- 309 evidently increased the protein expression of BDNF when Akt and CREB were activated. This function was antagonized by the addition of LY294002. Conclusion SMND- 309 can prevent neuronal cell death in vitro. This process may be related to the activation of the PI3K/Akt/CREB-signalling pathway.
引用
收藏
页码:1982 / 1990
页数:9
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