Prion peptide-mediated cellular prion protein overexpression and neuronal cell death can be blocked by aspirin treatment

Jeong, Jae‐Kyo; Moon, Myung‐Hee; Seol, Jae‐Won; Seo, Jae-Suk; Lee, You-Jin; Park, Sang-Youel

doi:10.3892/ijmm.2011.626

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…The proteins were resolved by 10–15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes and were analyzed by Western blotting, as described previously [48]. The immunoblotting antibodies were HIF-1α (BD Biosciences, San Diego, CA, USA), PrPc (Millipore, Milford, MA, USA), Bcl-2 (Santa Cruz Biotechnology, Santa Cruz, CA, USA), phosphorylated-Akt (p-Akt) (Cell Signaling Technology, Danvers, MA, USA), DR4, DR5, and β-actin (Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment

et al. 2015

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Hypoxia decreases cytotoxic responses to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. Cellular prion protein (PrPc) is regulated by HIF-1α in neurons. We hypothesized that PrPc is involved in hypoxia-mediated resistance to TRAIL-induced apoptosis. We found that hypoxia induced PrPc protein and inhibited TRAIL-induced apoptosis. Thus silencing of PrPc increased TRAIL-induced apoptosis under hypoxia. Overexpression of PrPc protein using an adenoviral vector inhibited TRAIL-induced apoptosis. In xenograft model in vivo, shPrPc transfected cells were more sensitive to TRAIL-induced apoptosis than in shMock transfected cells. Molecular chemo-therapy approaches based on the regulation of PrPc expression need to address anti-tumor function of TRAIL under hypoxia. Molecular chemo-therapy approaches based on the regulation of PrPc expression need to address anti-tumor function of TRAIL under hypoxia.

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Section: Methodsmentioning

confidence: 99%

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment

et al. 2015

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“…Therefore, PrP 106–126 is widely used as a model for studying PrP Sc neurotoxicity (Forloni et al ., 1993; Gu et al ., 2002; Jeong et al ., 2011). In parallel with PrP Sc , further investigation of the mechanism by which PrP Sc results in neuronal death could provide novel insights into therapeutic targets for prion (Zhu et al ., 2016).…”

Section: Introductionmentioning

confidence: 99%

DLP1‐dependent mitochondrial fragmentation and redistribution mediate prion‐associated mitochondrial dysfunction and neuronal death

Wang

et al. 2017

Aging Cell

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SummaryMitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin‐like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP106–126 in vitro as well as in prion strain‐infected hamster brain in vivo. Suppression of DLP1 expression by DPL1 RNAi inhibited prion‐induced mitochondrial fragmentation and dysfunction (measured by ADP/ATP ratio, mitochondrial membrane potential, and mitochondrial integrity). We also demonstrated that DLP1 RNAi is neuroprotective against prion peptide in N2a cells as shown by improved cell viability and decreased apoptosis markers, caspase 3 induced by PrP106–126. On the contrary, overexpression of DLP1 exacerbated mitochondrial dysfunction and cell death. Moreover, inhibition of DLP1 expression ameliorated PrP106–126‐induced neurite loss and synaptic abnormalities (i.e., loss of dendritic spine and PSD‐95, a postsynaptic scaffolding protein as a marker of synaptic plasticity) in primary neurons, suggesting that altered DLP1 expression and mitochondrial fragmentation are upstream events that mediate PrP106–126‐induced neuron loss and degeneration. Our findings suggest that DLP1‐dependent mitochondrial fragmentation and redistribution plays a pivotal role in PrPS c‐associated mitochondria dysfunction and neuron apoptosis. Inhibition of DLP1 may be a novel and effective strategy in the prevention and treatment of prion diseases.

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“…Proteins were subjected to 10-15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and subjected to western blotting as described previously [ 43 ]. Antibodies used for immunoblotting were specific for Bax (Santa Cruz Biotechnology, Santa Cruz, CA, USA); caspase-8, p62, LC3, ATG5 (Cell Signaling Technology, Danvers, MA, USA), DR4, DR5, and β-actin (Sigma-Aldrich, St Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Activation of autophagic flux by epigallocatechin gallate mitigates TRAIL-induced tumor cell apoptosis via down-regulation of death receptors

2016

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Epigallocatechin gallate (EGCG) is a major polyphenol in green tea. Recent studies have reported that EGCG can inhibit TRAIL-induced apoptosis and activate autophagic flux in cancer cells. However, the mechanism behind these processes is unclear. The present study found that EGCG prevents tumor cell death by antagonizing the TRAIL pathway and activating autophagy flux. Our results indicate that EGCG dose-dependently inhibits TRAIL-induced apoptosis and decreases the binding of death receptor 4 and 5 (DR4 and 5) to TRAIL. In addition, EGCG activates autophagy flux, which is involved in the inhibition of TRAIL cell death. We confirmed that the protective effect of EGCG can be reversed using genetic and pharmacological tools through re-sensitization to TRAIL. The inhibition of autophagy flux affects not only the re-sensitization of tumor cells to TRAIL, but also the restoration of death receptor proteins. This study demonstrates that EGCG inhibits TRAIL-induced apoptosis through the manipulation of autophagic flux and subsequent decrease in number of death receptors. On the basis of these results, we suggest further consideration of the use of autophagy activators such as EGCG in combination anti-tumor therapy with TRAIL.

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Prion peptide-mediated cellular prion protein overexpression and neuronal cell death can be blocked by aspirin treatment

Cited by 5 publications

References 23 publications

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment

DLP1‐dependent mitochondrial fragmentation and redistribution mediate prion‐associated mitochondrial dysfunction and neuronal death

Activation of autophagic flux by epigallocatechin gallate mitigates TRAIL-induced tumor cell apoptosis via down-regulation of death receptors

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