Glucagon-like peptide-1 protects the murine hippocampus against stressors via Akt and ERK1/2 signaling.
Glucagon-like peptide-1 protects the murine hippocampus against stressors via Akt and ERK1/2 signaling.
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DOI：
10.1016/j.bbrc.2015.01.098
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发表时间：
2015-03
影响因子：
3.1
通讯作者：
Y. Yoshino;M. Ishisaka;Saori Tsujii;M. Shimazawa;H. Hara
中科院分区：
文献类型：
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作者：
Y. Yoshino;M. Ishisaka;Saori Tsujii;M. Shimazawa;H. Hara
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是认知功能障碍和海马和大脑皮质神经元细胞死亡。胰高血糖素样肽-1（GLP-1）是一种促胰岛素分泌肽。GLP-1相关药物被广泛用于治疗2型糖尿病。此外，它们已被证明可以改善AD小鼠模型的病理学。在这里，我们研究了GLP-1对小鼠海马HT 22细胞中不同应激源的影响。GLP-1（7-36）以浓度依赖性方式阻止H2 O2、l-谷氨酸、衣霉素、毒胡萝卜素和淀粉样蛋白β1-42诱导的神经元细胞死亡。与溶剂处理相比，GLP-1（7-36）处理1小时显著增加磷酸化Akt和细胞外信号调节激酶1和2（ERK 1/2）。这些结果表明，GLP-1（7-36）通过激活生存信号分子（如HT 22细胞中的Akt和ERK 1/2）对这些应激物具有保护作用。总之，GLP-1和GLP-1受体激活剂可能是治疗AD的有用靶点。
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive dysfunction and neuronal cell death in the hippocampus and cerebral cortex. Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptides. GLP-1-associated medicines are widely used as treatments for type 2 diabetes. In addition, they have been shown to ameliorate pathology in AD mouse models. Here, we investigated the effects of GLP-1 on different stressors in murine hippocampal HT22 cells. GLP-1 (7–36) prevented H2O2-,l-glutamate-, tunicamycin-, thapsigargin-, and amyloid β1–42-induced neuronal cell death in a concentration-dependent manner. GLP-1 (7–36) treatment for 1 h significantly increased phosphorylated Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2) when compared with vehicle-treatment. These results suggest that GLP-1 (7–36) is protective against these stressorsviaactivation of survival signaling molecules, such as Akt and ERK1/2 in HT22 cells. In conclusion, GLP-1 and activators of the GLP-1 receptor might be useful targets for the treatment of AD.