Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Neurology Department of the Second Associated Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Drug Res (Stuttg). 2021 Jan;71(1):43-50. doi: 10.1055/a-1266-3263. Epub 2020 Oct 6.
Glucagon-like peptide-2 (GLP-2) is a peptide hormone that belongs to the glucagon-derived peptide family. We have previously shown that analogues of the sister hormone Glucagon-like peptide-1 (GLP-1) showed neuroprotective effects. Here we investigated the effect of a GLP-2 agonist in a cell model of Parkinson's disease (PD) created by treating SH-SY5Y or Neuro-2a cells with 1-Methyl-4-phenyl-pyridine ion (MPP+). Cell viability and cell cytotoxicity was detected by MTT and LDH assays, respectively. The protein expression levels of mitochondrial, autophagy and apoptotic biomarkers including PGC-1α, Mfn2, IRE1, ATG7, LC3B, Beclin1 and Bcl-2 were detected by western blot. Mitochondrial superoxide was detected by MitoSOX Red. In addition, mitochondrial morphology, autophagosome and apoptotic corpuscles were observed by transmission electron microscope (TEM). We found that the GLP-1 and the GLP-2 agonists both protect cells against mitochondrial damage, autophagy impairments and apoptosis induced by MPP+both in SH-SY5Y and Neuro-2a cells. Cell signaling for mitogenesis was enhanced, and oxidative stress levels much reduced by the drugs. This demonstrates for the first time the neuroprotective effects of a GLP-2 analogue in PD cellular models, in which oxidative stress, autophagy and apoptosis play crucial roles. The protective effects were comparable to those seen with the GLP-1 analogue liraglutide. The results suggest that not only GLP-1, but also GLP-2 has neuroprotective properties and may be useful as a novel treatment of PD.
胰高血糖素样肽-2（GLP-2）是一种肽类激素，属于胰高血糖素衍生肽家族。我们之前已经表明，类似物的姐妹激素胰高血糖素样肽-1（GLP-1）表现出神经保护作用。在这里，我们研究了 GLP-2 激动剂在帕金森病（PD）细胞模型中的作用，该模型是通过用 1-甲基-4-苯基-吡啶鎓离子（MPP+）处理 SH-SY5Y 或 Neuro-2a 细胞而创建的。通过 MTT 和 LDH 测定分别检测细胞活力和细胞细胞毒性。通过 Western blot 检测线粒体、自噬和凋亡生物标志物（包括 PGC-1α、Mfn2、IRE1、ATG7、LC3B、Beclin1 和 Bcl-2）的蛋白表达水平。通过 MitoSOX Red 检测线粒体超氧化物。此外，通过透射电子显微镜（TEM）观察线粒体形态、自噬体和凋亡小体。我们发现，GLP-1 和 GLP-2 激动剂都能保护细胞免受 MPP+诱导的线粒体损伤、自噬损伤和凋亡，无论是在 SH-SY5Y 还是 Neuro-2a 细胞中都是如此。细胞有丝分裂信号增强，药物大大降低了氧化应激水平。这首次证明了 GLP-2 类似物在 PD 细胞模型中的神经保护作用，其中氧化应激、自噬和凋亡起着至关重要的作用。保护作用与 GLP-1 类似物利拉鲁肽相当。结果表明，不仅 GLP-1，而且 GLP-2 都具有神经保护特性，可能作为 PD 的一种新的治疗方法有用。
