Drug Design, Development and Therapy (May 2020)
Glycine Improves Ischemic Stroke Through miR-19a-3p/AMPK/GSK-3β/HO-1 Pathway
Abstract
Zhong-Jun Chen, Xu-Sheng Zhao, Tie-Ping Fan, Heng-Xu Qi, Di Li Neurological Intervention Department, Dalian Municipal Central Hospital, Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Di LiNeurological Intervention Department, Dalian Municipal Central Hospital, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 411-84412001-8481Email [email protected]: To explore the molecular mechanism of glycine in improving ischemic stroke.Patients and Methods: The serum samples of patients with ischemic stroke and healthy people were compared. The ischemic stroke model of PC12 cells was established by oxygen-glucose deprivation (OGD). qPCR quantified miR-19a-3p and AMPK mRNA, and protein expression was detected by Western blot. MTT was used to detect cell activity. Flow cytometry was used to detect cells. Glucose metabolism kit was used to detect glucose intake and formation amount of lactic acid.Results: Compared with the control group, OGD group (OGDG) showed lower cell activity and increased cell apoptosis. TNF-α, IL-1βI, L-6, Caspase 3, Caspase 9 and Bax were up-regulated, and Glut1, HK2, LDHA, PDK1, PKM2 and Bcl2 were down-regulated. At the same time, glucose intake, formation amount of lactic acid and cell apoptosis rate were reduced, and AMPK/GSK-3β/HO-1 pathway activity was down-regulated. Glycine could counteract the above phenomena in OGDG. miR-19a-3p and AMPK decreased and increased, respectively, during glycine therapy. AMPK was the target gene of miR-19a-3p. Rescue experiments demonstrated that glycine improved cell apoptosis, inflammatory response and glucose metabolism disorder of ischemic stroke through miR-19a-3p/AMPK/GSK-3β/HO-1 pathway.Conclusion: Glycine improves ischemic stroke through miR-19a-3p/AMPK/GSK-3β/HO-1 pathway.Keywords: ischemic stroke, AMPK/GSK-3β/HO-1 pathway, miR-19a-3p, glycine
