A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury

Chen, Juan; Hu, Rong; Liao, Hua‐Bao; Zhang, Ya; Lei, Ruixue; Zhang, Zhifeng; Yang, Zhuang; Yu, Wenli; Park, Jin; Feng, Hua; Wan, Qi

doi:10.1038/s41598-017-03909-0

Cited by 45 publications

(49 citation statements)

References 53 publications

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“…Transient focal cerebral ischaemia was induced using the suture occlusion technique [ 20 , 21 ]. The whole process do as our lab described [ 22 ]. Male Sprague-Dawley rats weighing 250–300 g were anaesthetized with 4% isoflurane in 70% N 2 O and 30% O 2 by using a mask.…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as previously described [ 22 ]. Briefly, the polyvinylidene difluoride (PVDF) membrane by Millipore (USA) was used incubate with a first antibody against ERK 1/2 (Rabbit, 1:2000), phospho-ERK 1/2 (Thr 202 /Tyr 204 ) (Rabbit, 1:2000), PTEN (Rabbit, 1:1000), AKT (Mouse, 1:1000), phospho-AKT (Ser 473 ) (Rabbit, 1:2000), Actin (Rabbit, 1:2000) from Cell Signaling Technology (MA, USA).…”

Section: Methodsmentioning

confidence: 99%

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ERK 1/2 Activation Mediates the Neuroprotective Effect of BpV(pic) in Focal Cerebral Ischemia–Reperfusion Injury

et al. 2018

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Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is a commercially available PTEN inhibitor. Previous studies from us and others have shown that bpV(pic) confers neuroprotection in cerebral ischemia injury. We set up to determine whether ERK 1/2 activation plays a role in bpV(pic)-induced neuroprotective effect in cerebral ischemia injury. We found that the phosphorylation levels of Akt (p-AKT) and ERK1/2 (p-ERK 1/2) were down-regulated after cerebral ischemia–reperfusion injury. The injection of bpV(pic) after injury not only increased the level of p-AKT but also the level of p-ERK 1/2. While the inhibition of PTEN mediated the up-regulatation of p-AKT and p-ERK 1/2 by bpV(pic). Interestingly, the ERK 1/2 activation induced by bpV(pic) was also independent of the inhibition of PTEN. Our results indicate that bpV(pic) protects against OGD-induced neuronal death and promotes the functional recovery of stroke animals through PTEN inhibition and ERK 1/2 activation, respectively. This study suggests that the effect of bpV(pic) on ERK 1/2 signaling should be considered while using bpV(pic) as a PTEN inhibitor.Electronic supplementary materialThe online version of this article (10.1007/s11064-018-2558-z) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

ERK 1/2 Activation Mediates the Neuroprotective Effect of BpV(pic) in Focal Cerebral Ischemia–Reperfusion Injury

et al. 2018

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“…Western blotting was performed as previously described (33). Briefly, a polyvinylidene difluoride membrane from Millipore was used to incubate the samples with the primary Abs against NF-kB p65 (rabbit, 1:1000), Hif-1a (rabbit, 1:1000), AKT (mouse, 1:1000), phospho-AKT (Ser 473 ) (rabbit, 1:2000), PTEN (rabbit, 1:1000), and actin (rabbit, 1:2000) from Cell Signaling Technology.…”

Section: Western Blotting Analysismentioning

confidence: 99%

Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-κB p65/Hif-1α Signaling Pathway

Liao

Pan

et al. 2019

The Journal of Immunology

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Glycine is a simple nonessential amino acid known to have neuroprotective properties. Treatment with glycine results in reduced infarct volume of the brain, neurologic function scores, and neuronal and microglial death in ischemic stroke injury. Neuroinflammation has been considered a major contributor to cerebral ischemia–induced brain damage. However, the role of glycine in neuroinflammation following ischemic stroke is unclear. The present study aimed to determine whether neuroinflammation is involved in the neuroprotective effects of glycine in cerebral ischemia injury. Ischemic stroke promotes M1 microglial polarization. Interestingly, we found that the injection of glycine in rats after injury can inhibit ischemia-induced inflammation and promote M2 microglial polarization in vivo (Sprague–Dawley rats) and in vitro (cortical microglia and BV-2 cells). We show that glycine suppresses Hif-1α by inhibiting the upregulation of NF-κB p65 after ischemia-reperfusion injury, resulting in the inhibition of proinflammatory activity. The activation of AKT mediates the inhibition of NF-κB p65/Hif-1α signaling by glycine. Moreover, we confirm that glycine-regulated AKT activation is mediated by the inhibition of PTEN in a PTEN depletion cell line, U251 cells. Glycine modulates microglial polarization after ischemic stroke, which indirectly inhibits ischemia-induced neuronal death and functional recovery. Taken together, our findings provide a new understanding of glycine in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing NF-κB p65/Hif-1α signaling.

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“…Western blotting was performed as previously described [23]. Briefly, a polyvinylidene difluoride membrane from Millipore was used to incubate the samples with the primary HIF-1α (rabbit, 1:1000, MA1-516, Thermo Fisher, USA), LDHA (mouse, 1:500, sc137244, Santa Cruz, USA) and β-actin (rabbit, 1:2000, bs-0061R, Bioss, China).…”

Section: Western Blotting Analysismentioning

confidence: 99%

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

et al. 2020

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Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.

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A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury

Cited by 45 publications

References 53 publications

ERK 1/2 Activation Mediates the Neuroprotective Effect of BpV(pic) in Focal Cerebral Ischemia–Reperfusion Injury

ERK 1/2 Activation Mediates the Neuroprotective Effect of BpV(pic) in Focal Cerebral Ischemia–Reperfusion Injury

Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-κB p65/Hif-1α Signaling Pathway

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

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