Glycine confers neuroprotection through microRNA-301a/PTEN signaling.

Juan Chen,Zhi-Qiang Li,Zhi-Feng Zhang,Ping Jin,Guang-Ming Xia,Shu Wang,Yang Zhuang,Gang Li,Qi Wan,Ze-Fen Wang,Chunjiang He,Peng-Chao Hu,Yuan Wang

doi:10.1186/s13041-016-0241-3

Abstract

BackgroundGlycine is known to protect against neuronal death. However, the underlying mechanism remains to be elucidated. The microRNA-301a is involved in both biological and pathological processes. But it is not known whether microRNA-301a has a neuroprotective property. In this study, we aimed to determine whether glycine-induced neuroprotection requires microRNA-301a-dependent signaling.ResultsWe provided the first evidence that glycine increased the expression of microRNA-301a in cultured rat cortical neurons and protected against cortical neuronal death through up-regulation of microRNA-301a after oxygen-glucose deprivation. MicroRNA-301a directly bound the predicted 3′UTR target sites of PTEN and reduced PTEN expression in cortical neurons. We revealed that PTEN down-regulation by microRNA-301a mediated glycine-induced neuroprotective effect following oxygen-glucose deprivation.ConclusionsOur results suggest that 1) microRNA-301a is neuroprotective in oxygen-glucose deprivation-induced neuronal injury; 2) glycine is an upstream regulator of microRNA-301a; 3) glycine confers neuroprotection through microRNA-301a/PTEN signal pathway.

Highlights

Glycine is known to protect against neuronal death
We show that the expression of miR-301a is elevated by glycine. miR-301a mediates glycine-induced neuroprotective effect in cultured cortical neurons subjected to oxygen-glucose deprivation (OGD). miR-301a binds the predicted 3′-untranslated region (3′UTR) target sites of PTEN and reduces PTEN expression
To verify the neuroprotective role of glycine in our experimental conditions, we examined the effect of glycine on cultured cortical neurons subjected to OGD

Summary

Introduction

Glycine is known to protect against neuronal death. The microRNA-301a is involved in both biological and pathological processes. It is not known whether microRNA-301a has a neuroprotective property. Glycine is a co-agonist of the excitatory NMDA receptor, a calcium-permeable ion channel in the CNS [8, 9]. Down-regulation of PTEN is shown to protect against neuronal death through the enhancement of Akt activation, the inhibition of NR2B-containing NMDA receptors [18], the preservation of GABAA receptors and the up-regulation of TDP-43 [19, 20]. We have shown that NR2Acontaining NMDA receptors and DJ-1 exert their neuroprotective effects by down-regulating PTEN [20, 21]. Consistent with our findings, recent studies have revealed that PTEN down-regulation is neuroprotective in

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