Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ 1-42 -induced neurotoxicity via activating the JAK2/STAT3 axis

Wang, Ke; Xie, Minhao; Zhu, Ling; Zhu, Xue; Zhang, Kai; Zhou, Fanfan

doi:10.5114/fn.2015.54423

Cited by 20 publications

(12 citation statements)

References 41 publications

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“…METH-induced apoptosis in neuronal cells is associated with the activation of NF-κB, STAT3, and MAPK-ERK signaling [ 15 , 18 , 38 ]. We first analyzed the caspase-3 (17 kDa) and PARP (89 kDa) expression to understand the neurotoxic effects of METH on the growth of dopaminergic SH-SY5Y cells (Additional file 5 : Figure S5).…”

Section: Resultsmentioning

confidence: 99%

“…METH is able to induce pro-inflammatory cytokines and mediators through the NF-κB and STAT3 pathways in dopaminergic and microglia cells [ 9 , 15 , 39 ]. The potential involvement of NF-κB and STAT3 was investigated because the promoters of both TNFα and IL-6 contain binding sites for NF-κB and STAT3, which are known to be involved in neurological disorders associated with increased inflammation [ 14 , 18 ]. In accordance with these findings, our results showed that AA effectively inhibits nuclear translocation of NF-κB (p65) and STAT3 in METH-stimulated dopaminergic SH-SY5Y cells, mesencephalic neurons, and BV2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of TNFR stimulates several signaling pathways that regulate cellular processes, ranging from cell proliferation and differentiation to cell death [ 16 ]. With respect to IL-6, its production seems to be regulated by several signaling cascades [ 9 , 17 ], including TNF-α activation via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT) signaling pathways [ 14 , 15 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Park

Seo

Jang

et al. 2017

J Neuroinflammation

115

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BackgroundMethamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway.MethodsWe used the human dopaminergic neuroblastoma SH-SY5Y cell line, murine microglial BV2 cell line, and primary culture of rat embryo mesencephalic neurons. Pro-inflammatory cytokine production was monitored by ELISA and RT/real-time PCR. The cell cycle distribution and mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting, DNA-binding activity, and immunofluorescence staining to analyze the effect of AA on activation of the NF-κB, STAT3, MAPK-ERK, and apoptosis signaling pathways.ResultsMETH induced TNF receptor (TNFR) expression and led to morphological changes of cells. Additionally, this drug increased pro-inflammatory cytokine (TNFα and IL-6) expression. AA significantly suppressed METH-induced TNFR expression in concentration dependent. Increased secretion of TNFα and IL-6 was inhibited in METH-stimulated neuronal cells by AA administration. AA showed significant protection against METH-induced translocation of NF-κB/STAT3 and ERK phosphorylation. AA inhibited METH-induced proteolytic fragmentation of caspase-3 and PARP. The pro-apoptotic protein Bax was significantly decreased, while the anti-apoptotic protein Bcl-xL was increased by AA treatment in METH-stimulated cells. A similar protective effect of AA on mitochondrial membrane integrity was also confirmed by flow cytometry and immunofluorescence staining.ConclusionsBased on the literatures and our findings, AA is a promising candidate for an anti-neurotoxic agent, and it can potentially be used for the prevention and treatment of various neurological disorders.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1009-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Park

Seo

Jang

et al. 2017

J Neuroinflammation

115

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“…AD is associated with the production and deposition of Aβ and phosphorylated tau in APs and NFTs (1). The overloading of aggregated Aβ and phosphorylated tau will induce excessive toxicity to the neurons, which results in impairing the brains of AD patients (39,40). For neuroprotection, PGA1 has been reported to blunt N-methyl-D-aspartate receptor (NMDAR)-mediated neuronal apoptosis and inhibits enhancement of the intracellular calcium concentration, TXA 2 production, and platelet activation in rodent models of stroke (41).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin A1 inhibits the phosphorylation of tau via activating protein phosphotase 2A in a michael addition mechanism at the site of cysteine 377

Guan

Wang

2020

Preprint

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Background: Prostaglandin (PG) A1 is a metabolic product of cyclooxygenase 2 (COX-2), which potentially involved in regulating the development and progression of Alzheimer’s disease (AD). As a cyclopentenone (cy) PG, PGA1 is characterized by the presence of a chemically reactive α, β-unsaturated carbonyl. Although PGA1 is potentially involved in regulating multiple biological processes via michael addition, its specific roles in AD remained unclear.Methods: The tauP301S transgenic (Tg) mice were employed as in vivo AD models and neuroblastoma (N) 2a cells as in vitro neuronal models. By intracerebroventricular injected (i.c.v) with PGA1, the binding proteins to PGA1 are analyzed by HPLC-MS-MS. In addition, western blots are used to determine the phosphorylation of tau in PGA1 treated Tg mice in the absence or presence of okadaic acid (OA), an inhibitor of protein phosphotase (PP) 2A. Combining a synthesis of pull down assay, immunoprecipitation, western blots and HPLC-MS-MS, PP2A scaffold subunit A alpha (PPP2R1A) was identified to be activated by directly binding on PGA1 in cysteine 377-dependent manner. Via inhibiting the hyperphosphorylation of tau, morris maze test was employed to determine the inhibitory effects of PGA1 on cognitive decline of tauP301S Tg mice.Results: By incubation with neuroblastoma (n)2a cells and pull down assay, mass spectra (MS) analysis revealed that PGA1 binds with more than 1000 proteins, among which contains the proteins of AD, especially tau protein. Moreover, short-term administration of PGA1 to tauP301S Tg mice significantly decreased the phosphorylation of tau at the sites of Thr181, Ser202 and Ser404 in a dose-dependent manner. To the reason, it’s caused by activating PPP2R1A in tauP301S Tg mice. More importantly, PGA1 has the ability to form michael adduct with PPP2R1A via its cysteine 377 motif, which is critical for the enzymatic activity of PP2A. By activating PP2A, long-term application of PGA1 to tauP301S Tg mice significantly reduced the phosphorylation of tau, which results in improving the cognitive decline of tauP301S Tg mice.Conclusion: Our data provided the first insights needed to decipher the mechanisms underlying the ameliorating effects of PGA1 on cognitive decline of tauP301S Tg mice via activating PP2A in a PPP2R1AC377-dependent Michael adducting mechanisms.

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“…Tong et al have demonstrated that NgR silencing inhibits C6 cell proliferation and promotes cell apoptosis ( 21 ). Wang et al have reported that CNTF protects neuroblastoma SH-SY5Y cells from cytotoxicity and apoptosis induced by amyloid beta peptide (Aβ 1–42 ) ( 22 ). However, the effect of NgR knockdown or CNTF treatment and their synergistic effect on RGC-5 cells needed to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Nogo receptor knockdown and ciliary neurotrophic factor attenuate diabetic retinopathy in streptozotocin-induced diabetic rats

Guo

Liu

2017

Molecular Medicine Reports

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Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). We investigated whether Nogo receptor (NgR) knockdown and ciliary neurotrophic factor (CNTF) treatment, either alone or in combination, ameliorated diabetic retinopathy (DR) in diabetic rat model. STZ-induced diabetic rats were administrated for a total of 12 weeks with 3 µM siRNA (5 µl) once every 6 weeks and/or 1 µg CNTF weekly. The retinal tissues were excised. We measured cell number in ganglion cell layer (GCL) using H&E staining and cell apoptosis using TUNEL assay. Bax, Bcl-2, Caspase-3, F-actin, GAP-43, NgR, RhoA and Rock1 levels were then analyzed by Western blotting, Immunohistochemistry or Real-time PCR. We found that NgR siRNA or CNTF injection alone significantly increased cell count in GCL in diabetic rats, inhibited ganglion cell apoptosis, elevated Bcl-2, F-actin and GAP-43, and decreased Bax, Caspase-3, NgR, RhoA and Rock1 levels. Combination treatment further prevented retinal ganglion cell loss, enhanced growth cone cytoskeleton and axonal regeneration, and suppressed NgR/RhoA/Rock1. Our results indicate that combination therapy has therapeutic potential for the treatment of DR.

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Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ 1-42 -induced neurotoxicity via activating the JAK2/STAT3 axis

Cited by 20 publications

References 41 publications

Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway

Prostaglandin A1 inhibits the phosphorylation of tau via activating protein phosphotase 2A in a michael addition mechanism at the site of cysteine 377

Nogo receptor knockdown and ciliary neurotrophic factor attenuate diabetic retinopathy in streptozotocin-induced diabetic rats

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