Glial cell line‐derived neurotrophic factor alters lipid composition and protein distribution in MPP+‐injured differentiated SH‐SY5Y cells

Mu, Peipei; Liu, Yuting; Jiang, Shanwen; Gao, Jin; Sun, Shuang; Li, Li; Gao, Dayong

doi:10.1002/jcp.29738

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…It has been shown that, in a variety of neurodegenerative diseases, such as PD, Alzheimer's disease and familial amyotrophic lateral sclerosis, lipid rafts appear to have abnormal lipid composition and functional de ciencies in the brain, which can promote the pathogenesis and development of these diseases [36][37][38] . Our previous study also showed that the lipid and protein components of lipid rafts were signi cantly altered in MPP + -induced PD cell models [39] . Furthermore, studies of various unit membrane models have shown that GM1 can affect the phase separation of lipid membranes and the assembly of microdomains [22,24,40,41] .…”

Section: Discussionmentioning

confidence: 82%

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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Section: Discussionmentioning

confidence: 82%

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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“…20,21) Some secreted factors are known to affect the lipid composition of the brain. [22][23][24] Among those factors, a secreted glycoprotein Reelin contributes to increased levels of polyunsaturated fatty acids in neurons, 23) which may partly explain why Reelin induces dendrite elongation. [25][26][27] However, how neurons regulate plasma membrane polarity is not understood.…”

Section: Discussionmentioning

confidence: 99%

The Plasma Membrane Polarity Is Higher in the Neuronal Growth Cone than in the Cell Body of Hippocampal and Cerebellar Granule Neurons

Oya,

Korogi,

Kohno

et al. 2023

Biological & Pharmaceutical Bulletin

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The polarity of the biological membrane, or lipid order, regulates many cellular events. It is generally believed that the plasma membrane polarity is regulated according to cell type and function, sometimes even within a cell. Neurons have a variety of functionally specialized subregions, each of which bears distinct proteins and lipids, and the membrane polarity of the subregions may differ accordingly. However, no direct experimental evidence of it has been presented to date. In the present study, we used a cell-impermeable solvatochromic membrane probe NR12A to investigate the local polarity of the plasma membrane of neurons. Both in hippocampal and cerebellar granule neurons, growth cones have higher membrane polarity than the cell body. In addition, the overall variation in the polarity value of each pixel was greater in the growth cone than in cell bodies, suggesting that the lateral diffusion and/or dynamics of the growth cone membrane are greater than other parts of the neuron. These tendencies were much less notably observed in the lamellipodia of a non-neuronal cell. Our results suggest that the membrane polarity of neuronal growth cones is unique and this characteristic may be important for its structure and function.

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“…GDNF is a family of neurotrophins with similarities to the transforming growth factor β regulatory proteins ( 11 , 35 ) and it has been identified as a potent neurotrophic factor for a variety of neuronal cell populations ( 36 ). GDNF is biosynthesized in glial cells and might be relevant to the development of gliomas ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1

Wang

et al. 2022

Int J Oncol

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Cancer cells rewire their metabolism to meet the demands of growth and survival and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. However, the respective mechanisms remain elusive and the contribution of aberrant lipid metabolism to the malignant phenotypes of glioma are unclear. The present study demonstrated that glial-derived neurotrophic factor (GDNF) is highly expressed in glioma and associated with poor clinical outcomes. In addition, there was a significant correlation between GDNF/rearranged during transfection (RET)/ERK signaling and sterol regulatory element-binding protein-1 (SREBP-1) expression in glioma cells. Pharmacological or genetic inhibition of GDNF-induced RET/ERK activity downregulated SREBP-1 expression and SREBP-1-mediated transcription of lipogenic genes. Additionally, GDNF regulated SREBP-1 activity by promoting hypoxia-inducible factor-1α (HIF-1α) mediated glucose absorption and hexosamine biosynthetic pathway mediated SREBP cleavage-activating protein N-glycosylation. In addition, the inhibition of SREBP-1 reduced the in vitro GDNF-induced glioma cell proliferation. The results elucidated the complex relationship between GDNF/RET/ERK signaling and dysregulated glycolipid-metabolism, which shows great potential to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.

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Glial cell line‐derived neurotrophic factor alters lipid composition and protein distribution in MPP+‐injured differentiated SH‐SY5Y cells

Cited by 4 publications

References 57 publications

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

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

The Plasma Membrane Polarity Is Higher in the Neuronal Growth Cone than in the Cell Body of Hippocampal and Cerebellar Granule Neurons

GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1

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