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rLj-RGD3,一种源自[具体来源未给出]的含新型三RGD基序的重组蛋白,可保护PC12细胞免受氧葡萄糖剥夺和再灌注诱导的损伤。

rLj-RGD3, a Novel Three-RGD-Motif-Containing Recombinant Protein from , Protects PC12 Cells from Injury Induced by Oxygen-Glucose Deprivation and Reperfusion.

作者信息

Lv Li, Lu Qian, Shao Fangyu, Li Weiping, Zhou Qin, Wang Jihong, Li Qingwei

机构信息

School of Life Sciences, Liaoning Normal University, Dalian, Liaoning 116029, China; Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, China.

Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, China; College of Basic Medicine, Jilin Medical University, Jilin, Jilin 132013, China.

出版信息

Biomed Res Int. 2016;2016:6701249. doi: 10.1155/2016/6701249. Epub 2016 Sep 5.

Abstract

rLj-RGD3 is a 14.5 kDa recombinant protein with 3 RGD (Arg-Gly-Asp) motifs from the salivary gland secretions of , which is a histidine-rich and arginine-rich protein. Previous reports indicated that rLj-RGD3 has typical functions of RGD-toxin protein, such as platelet aggregation suppression tumour metastasis and angiogenesis inhibition. Because histidine and arginine have cerebral ischemia-reperfusion and neuroprotective functions, we investigated whether rLj-RGD3 has such activities and studied the mechanism. The effects of rLj-RGD3 on neuroprotection and antiapoptosis were determined. The expression level of focal adhesion kinase (FAK), p-FAK, Caspase-3, and Bcl-2 after oxygen-glucose deprivation and reperfusion (OGD-R) was examined. The viability of PC12 cells incubated with rLj-RGD3 at high concentrations (16 mol/L) increased significantly due to its ability to protect the cells from apoptosis after OGD-R-induced injury. Furthermore, rLj-RGD3 attenuated the damage due to OGD-R. Most of the PC12 cells were apoptotic after OGD-R. In contrast, the number of apoptotic PC12 cells was significantly decreased in the group treated with a high-dose of rLj-RGD3. In addition, rLj-RGD3 activated FAK and p-FAK protein. rLj-RGD3 inhibited Caspase-3 and upregulated Bcl-2 protein expression in PC12 cells after OGD-R. The study provides the first evidence for neuroprotective effects of rLj-RGD3 in ischemic injury that may be partly mediated through inhibition of Caspase-3 and upregulation of Bcl-2, FAK, and p-FAK protein expression.

摘要

rLj-RGD3是一种14.5 kDa的重组蛋白,具有来自唾液腺分泌物的3个RGD(精氨酸-甘氨酸-天冬氨酸)基序,是一种富含组氨酸和精氨酸的蛋白质。先前的报道表明,rLj-RGD3具有RGD毒素蛋白的典型功能,如抑制血小板聚集、肿瘤转移和血管生成。由于组氨酸和精氨酸具有脑缺血再灌注和神经保护功能,我们研究了rLj-RGD3是否具有此类活性并探讨了其机制。确定了rLj-RGD3对神经保护和抗凋亡的作用。检测了氧糖剥夺和再灌注(OGD-R)后粘着斑激酶(FAK)、磷酸化FAK(p-FAK)、半胱天冬酶-3(Caspase-3)和Bcl-2的表达水平。高浓度(16 μmol/L)的rLj-RGD3孵育PC12细胞后,其活力显著增加,因为它能够保护细胞免受OGD-R诱导的损伤后的凋亡。此外,rLj-RGD3减轻了OGD-R造成的损伤。OGD-R后大多数PC12细胞发生凋亡。相比之下,高剂量rLj-RGD3处理组的凋亡PC12细胞数量显著减少。此外,rLj-RGD3激活了FAK和p-FAK蛋白。OGD-R后,rLj-RGD3抑制PC12细胞中的Caspase-3并上调Bcl-2蛋白表达。该研究首次提供了rLj-RGD3在缺血性损伤中具有神经保护作用的证据,其机制可能部分是通过抑制Caspase-3以及上调Bcl-2、FAK和p-FAK蛋白表达来介导的。

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