MiR-122-5p Mitigates Inflammation, Reactive Oxygen Species and SH-SY5Y Apoptosis by Targeting CPEB1 After Spinal Cord Injury Via the PI3K/AKT Signaling Pathway

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

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Mining novel natural reactive oxygen species (ROS) inhibitors by targeting Rho Kinase for prevention of secondary spinal cord injury: An in-silico trial using traditional Chinese medicinal compounds

Journal of King Saud University - Science ◽

10.1016/j.jksus.2020.03.039 ◽

2020 ◽

Vol 32 (5) ◽

pp. 2540-2552

Author(s):

Lei Fang ◽

Ziliang Shen ◽

Shengming Xu ◽

Yu Chen ◽

Shuqiang Wang

Keyword(s):

Reactive Oxygen Species ◽

Spinal Cord ◽

Spinal Cord Injury ◽

In Silico ◽

Rho Kinase ◽

Reactive Oxygen ◽

Oxygen Species ◽

Medicinal Compounds ◽

Cord Injury ◽

Secondary Spinal Cord Injury

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Reactive oxygen species (ROS) modulate recovery of locomotion and central neuropathic pain following spinal cord injury

Journal of Pain ◽

10.1016/j.jpain.2011.02.174 ◽

2011 ◽

Vol 12 (4) ◽

pp. P43

Author(s):

Y. Gwak ◽

S. Hassler ◽

C. Hulsebosch

Keyword(s):

Reactive Oxygen Species ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Reactive Oxygen ◽

Oxygen Species ◽

Central Neuropathic Pain ◽

Cord Injury

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Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury

Experimental Neurology ◽

10.1016/j.expneurol.2004.05.046 ◽

2004 ◽

Vol 190 (2) ◽

pp. 414-424 ◽

Cited By ~ 24

Author(s):

R. de Castro ◽

M.G. Hughes ◽

G.-Y. Xu ◽

C. Clifton ◽

N.Y. Calingasan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Reactive Oxygen ◽

Oxygen Species ◽

Cord Injury

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Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

10.21203/rs.3.rs-38209/v1 ◽

2020 ◽

Author(s):

Xu Yan ◽

Yong Cao ◽

Chunyuan Chen ◽

Hui Xie ◽

Hongbin Lu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Signaling Pathway ◽

Functional Recovery ◽

Umbilical Vein ◽

Motor Evoked Potential ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Cord Injury

Abstract Background: Spinal cord injury (SCI) is a devastating clinical diseasewithout effectivetherapeuticapproach recently. In this study, we aim to investigate the effect of locally injection with exosome derived human urine stem cell (USC) embedding with hydrogelcould improve the spinal cord functional recovery after injury and the underlying mechanism.Methods:Exosome were isolate from USC andidentified by transmission electron microscopy and western blot. Functional assays using human umbilical vein endothelial cell (HUVEC) in vitro were performed to assess the effects of USC-Exosdeliverythe angiopoietin-like protein 3 (ANGPTL3) on tube formation and migration as well as their regulatory role in the PI3K/AKT signaling pathway activation. In vivo experiment we locally injection with exosome derived USC embedding with hydrogel for treatment of SCI. The effects of USC-Exos on functional recovery in spinal cord injury mice were tested by measuring motor evoked potential, histological and neovascular numbers. Meanwhile, the role of the candidate protein ANGPTL3 in USC-Exo for promoting angiogenesisin SCI was assessed.Results:In current study, we demonstrate that when given locallyinjection with exosomederivedhuman urine stem cell (USC) embeddingwith hydrogelcould pass the spinal cord blood brain barrier and delivery the angiopoietin-like protein 3 (ANGPTL3) to the injured spinal cord region. In addition, the administration of exosome derived from human USC could enhance spinal cord neurological functional recovery by promoting angiogenesis.The mechanism studies revealed that ANGPTL3 are enriched in USCexosome(USC-Exo) and required for USC exosome promoting angiogenesis. Functional studies further confirmed the effects caused by exosome derived from USC on angiogenesis wasmediated by PI3K/AKT signaling pathway. Conclusion:Collectively, our results indicated that USC derived exosome serve as a critical regulator of angiogenesis by transferring ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

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