The Actin Cytoskeleton Is Involved in Glial Cell Line-Derived Neurotrophic Factor (GDNF)-Induced Ret Translocation into Lipid Rafts in Dopaminergic Neuronal Cells

Li, Li; Song, Haijing; Mu, Peipei; Xu, Ming; Liu, Chaoxia; Wang, Ying; Qin, Ying‐Song; Sun, Shuang; Gao, Jin; Wang, Ting; Gao, Dayong

doi:10.3390/ijms18091922

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…The reagents used in the medium configuration were provided by Shanghai Beyotime Biotechnology Co., Ltd. from China. Twenty-four hours after modeling, OGD/R cells were treated with 50, 100, and 200 nM JAS pre-dissolved in dimethyl sulfoxide (abs9184, Absin, Shanghai, China) for 24 h (Li et al, 2017).…”

Section: Ogd/r Modeling and Cell Treatmentmentioning

confidence: 99%

Jasminoidin reduces ischemic stroke injury by regulating microglia polarization via PASK‐EEF1A1 axis

Wu,

Mao,

et al. 2023

Chem Biol Drug Des

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Jasminoidin (JAS) can alleviate ischemic stroke (IS) injury, but its molecular mechanism remains undefined. The polarization of microglia affects IS process. This research is powered to probe whether the molecular mechanism of JAS for IS treatment is coupled with microglia polarization. IS modeling in mice was accomplished by middle cerebral artery occlusion (MCAO) and model mice were injected with 25 and 50 mg/mL JAS, followed by determination of infarct volume, brain water content, and histological changes in mouse brains. The microglia modeling was performed by 1‐h oxygen–glucose deprivation and 24‐h reoxygenation. Oxygen–glucose deprivation/reoxygenation (OGD/R)‐induced microglia were treated with JAS and transfected with Per‐Arnt‐Sim kinase (PASK)‐overexpressing plasmid, subsequent to which cell viability and lactate dehydrogenase (LDH) level were determined. The mRNA or protein expressions of examined genes in microglia and brain tissues were detected by quantitative real‐time polymerase chain reaction or western blot. MCAO‐induced massive infarction, edema, and injury in mouse brain tissues, upregulated interleukin‐1 beta (IL‐1β), FcγRIIB (CD32), tumor necrosis factor alpha (TNF‐α), PASK, p‐eukaryotic elongation factor 1A1 (EEF1A1), and p‐EEF1A1/EEF1A1 levels, but downregulated mannose receptor 1 (CD206), arginase‐1 (Arg‐1) and interleukin‐10 (IL‐10), and EEF1A1 expressions, which was reversed by JAS. OGD/R treatment decreased microglial viability as well as expressions of CD206, Arg‐1, IL‐10, and EEF1A1, yet increased cytotoxicity and levels of IL‐1β, CD32, TNF‐α, PASK, p‐EEF1A1, and p‐EEF1A1/EEF1A1, which was reversed by JAS. PASK overexpression reversed the effects of JAS on microglia. JAS reduces IS injury by regulating microglia polarization via PASK‐EEF1A1 axis.

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Section: Ogd/r Modeling and Cell Treatmentmentioning

confidence: 99%

Jasminoidin reduces ischemic stroke injury by regulating microglia polarization via PASK‐EEF1A1 axis

Wu,

Mao,

et al. 2023

Chem Biol Drug Des

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“…GDNF has a unique receptor system that consists of the transmembrane signal transduction receptor RET and the ligand binding receptor GFRα1 [12] . Lipid rafts play a vital role in the transmission of GDNF signals [13][14][15] . Lipid rafts are highly dynamic membrane microdomains enriched in cholesterol and spingolipids, and they are in liquid-ordered (Lo) phases with lower membrane uidity than surrounding cell membranes [16,17] .…”

Section: Introductionmentioning

confidence: 99%

“…We and others showed that in the absence of GDNF, the signal transduction receptor RET is mainly located outside of lipid rafts [18] . After stimulation with GDNF, RET is translocated into lipid rafts, and multiple downstream effectors are recruited to activate RAS/Erk, PI3K/Akt and other signal transduction pathways involved in the regulation of cell survival, differentiation, migration, growth and other biological processes [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Monosialoganglioside GM1 Deficiency Inhibits the Neurotrophic Effects of GDNF by Disrupting Lipid Raft Assembly

Jiang

Zhou

Zhang

et al. 2021

Preprint

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Recent studies have shown that monosialoganglioside GM1 deficiency can inhibit the signal transduction process of glial cell line-derived neurotrophic factor (GDNF), which plays an important role in the pathogenesis of Parkinson's disease (PD). However, its specific mechanism still needs to be explored. We inhibited the expression of GM1 by treating cells with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). CCK-8 assay, EdU cell proliferation assay and Western blot assay were used to evaluate the effect of GM1 deficiency on the proliferation and differentiation of SH-SY5Y cells induced by GDNF and on the GDNF-RET signaling pathway. Lipid rafts were isolated by Triton X-100 solubilization and OptiPrepTM density gradient centrifugation. The alterations of lipid raft assembly and the translocation of RET into lipid rafts were evaluated after PDMP treatment. We found that PDMP treatment inhibited the proliferation and differentiation of SH-SY5Y cells induced by GDNF and reduced the phosphorylation of RET and its downstream signaling molecules Erk and Akt. In addition, after PDMP treatment, caveolin-1 and flotillin-1, the prototypical markers of lipid rafts, diffused from lipid rafts to non-lipid raft microdomains, and GDNF-induced RET translocation into lipid rafts was also reduced. These alterations could be partially reversed by adding exogenous GM1. Our results suggest that ganglioside GM1 deficiency could compromise the neurotrophic effects and signals downstream of GDNF by altering the assembly of lipid raft membrane microdomains.

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The reversible effects of glial cell line–derived neurotrophic factor (GDNF) in the human brain

Ayanlaja

Zhang

et al. 2018

Seminars in Cancer Biology

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Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor, and a member of the transforming growth factor β (TGF-β) superfamily acting on different neuronal activities. GDNF was originally identified as a neurotrophic factor crucially involved in the survival of dopaminergic neurons of the nigrostriatal pathway and is currently an established therapeutic target in Parkinson's disease. However, GDNF was later reported to be highly expressed in gliomas, especially in glioblastomas, and was demonstrated as a potent proliferation factor involved in the development and migration of gliomas. Here, we review our current understanding and progress made so far by researchers in our laboratories with references to relevant articles to support our discoveries. We present past and recent discoveries on the mechanisms involved in the protection of neurons by GDNF and examine its emerging roles in gliomas, as well as reasons for the abnormal expression in Glioblastoma Multiforme (GBM). Collectively, our work establishes a paradigm by which the ability of GDNF to protect dopaminergic neurons from degradation and its corresponding effects on glioma cells points to an underlying biological vulnerability in the effects of GDNF in the normal brain which can be subverted for use by cancer cells. Hence, presenting novel opportunities for intervention in glioma therapies.

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The Actin Cytoskeleton Is Involved in Glial Cell Line-Derived Neurotrophic Factor (GDNF)-Induced Ret Translocation into Lipid Rafts in Dopaminergic Neuronal Cells

Cited by 4 publications

References 32 publications

Jasminoidin reduces ischemic stroke injury by regulating microglia polarization via PASK‐EEF1A1 axis

Jasminoidin reduces ischemic stroke injury by regulating microglia polarization via PASK‐EEF1A1 axis

Monosialoganglioside GM1 Deficiency Inhibits the Neurotrophic Effects of GDNF by Disrupting Lipid Raft Assembly

The reversible effects of glial cell line–derived neurotrophic factor (GDNF) in the human brain

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