<p>Glycine Improves Ischemic Stroke Through miR-19a-3p/AMPK/GSK-3β/HO-1 Pathway</p>

Abstract

Purpose: 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 oxygenglucose 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 upregulated, 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.

Glycinergic Signaling in Macrophages and Its Application in Macrophage-Associated Diseases

“…MiR-19a-3p can suppress LPS/IFN-g-induced M1 macrophage polarization via inhibiting STAT1 (signal transducer and activator of transcription-1) (60). In addition, glycine regulates miR-19a-3p/AMPK pathway to alleviate ischemic stroke injury (61). Therefore, glycine may promote M1 macrophage polarization by regulating miR-19a-3p (Figure 2C).…”

Dysregulation Serum miR-19a-3p is a Diagnostic Biomarker for Asymptomatic Carotid Artery Stenosis and a Promising Predictor of Cerebral Ischemia Events

“… 12 More importantly, in transient ischemic attack (TIA), a complication of CAS, glycine improves TIA by regulating miR-19a-3p to inhibit glucose metabolism, inflammation, and apoptosis. 13 …”

“…12 More importantly, in transient ischemic attack (TIA), a complication of CAS, glycine improves TIA by regulating miR-19a-3p to inhibit glucose metabolism, inflammation, and apoptosis. 13 Although the function of miR-19a-3p in CAS-related diseases has been described in detail, the clinical potential of miR-19a-3p in asymptomatic CAS remains unknown. Therefore, according to the current research status of CAS, we examined the serum miR-19a-3p levels of recruited asymptomatic CAS patients and healthy subjects.…”

Protective Effect of An-Gong-Niu-Huang Wan Pre-treatment Against Experimental Cerebral Ischemia Injury via Regulating GSK-3β/HO-1 Pathway

“…It has been proven in many studies that inhibition of GSK-3β effectively upregulates HO-1 protein expression (Jiang et al, 2015;Yan et al, 2020). As a result, enhancement of HO-1 via GSK-3β inactivation (GSK-3β/ HO-1 pathway) plays a crucial role in improving ischemic stroke (Chen et al, 2020). In summary, HO-1 up-regulation is an adaptive response to oxidative stress in the body.…”

“…Specifically, upregulation of heme oxygenase-1 (HO-1) via GSK-3β deactivation through Ser9 phosphorylation could remarkably suppress the oxidative stress damage (Duan et al, 2019). It has been reported that glycine improved ischemic stroke via activation of the GSK-3β/HO-1 pathway (Chen et al, 2020). These studies suggested that the diminution of oxidant stress by activation of GSK-3β/HO-1 pathway is an effective therapeutic strategy for ischemic stroke prevention and treatment.…”