Glycine Dehydrogenase Mediates The Neuroprotective Effect Of Glycine In The Cell

ObjectiveGlycine has been shown to confer a neuroprotective effect through NMDAR and GlyR,but the intracellular role of glycine is not clear in CNS.In this study,we will detect the levels of glycine in brain tissue and neurons and explore the necessity and feasibility of supplementing glycine after stroke.The mechanism of glycine in the cells will also be researched to enrich the theory of glycine therapy for stroke.MethodsThe levels of glycine in normal and ischemic brain tissues were detected by high performance liquid chromatography(HPLC).We determinate the intracellular glycine levels in neuron by HPLC and immunofluorescence assay.The effect of exogenous glycine on the volume of ischemic injury was measure by TTC staining.MTT and LDH were used to detect the activity and death of primary cortical neurons in rats.Western blot was used to detect the expression of related proteins.Immunofluorescence was used to detect the distribution of proteins in primary neurons and brain.Results1.Glycine concentration was increased in brain but decreased in neurons after ischemia-reperfusion injury and OGD insult2.Glycine was decreased in neurons after OGD insult3.Glycine treatment reduces infarct volume and increases neuronal viability4.Expression of GLDC was decreased after ischemia-reperfusion injury and OGD insult5.Knocking down GLDC retarded glycine function of promoting neurons survival6.Inhibition of p53 up-regulated expression of GLDC7.Elevating GLDC through inhibiting p53 enhanced neuroprotection of glycineConclusions1.After cerebral ischemia injury,glycine concentration is increased in brain but reduced in the neurons2.Glycine alleviates ischemia injury and neuronal damage3.The glycine neuroprotection depends on GLDC expression.Low-GLDC detards glycine neuroprotection,on the contrary,glycine neuroprotection is enhances.4.The inhibition of p53 up-regulates GLDC expression which promotes the glycine neuroprotection...