ArticleMolecular and cellular biochemistry2010
Use of pifithrin to inhibit p53-mediated signalling of TNF in dystrophic muscles of mdx mice.
Article in Molecular and cellular biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Transcriptomic analysis of paired healthy human skeletal muscles to identify modulators of disease severity in DMD.Frontiers in genetics · 2023Article
- Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy: An assessment using the mdx model and human muscle.Muscle & nerve · 2022Article
- Article
- p53-PGC-1α pathway mediates oxidative mitochondrial damage and cardiomyocyte necrosis induced by monoamine oxidase-A upregulation: role in chronic left ventricular dysfunction in mice.Antioxidants & redox signaling · 2013Article
- Pro-apoptotic Effect of Pifithrin-α on Preimplantation Porcine In vitro Fertilized Embryo Development.Asian-Australasian journal of animal sciences · 2012Article
- PDGF-B-mediated downregulation of miR-21: new insights into PDGF signaling in glioblastoma.Human molecular genetics · 2012Article
- Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between exercise parameters and exacerbation of the dystrophic phenotype.PLoS currents · 2011Article
- Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells.British journal of pharmacology · 2011Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour Necrosis Factor (TNF) plays a major role in exacerbating necrosis of dystrophic muscle; however, the precise molecular mechanism underlying this effect of TNF is unknown. This study investigates the role that p53 plays in TNF-mediated necrosis of dystrophic myofibres by inhibiting p53 using pifithrin-alpha and three pifithrin-beta analogues. Tissue culture studies using C2C12 myoblasts established that pifithrin-alpha was toxic to differentiating myoblasts at concentrations greater than 10 muM. While non-toxic concentrations of pifithrin-alpha did not prevent the TNF-mediated inhibition of myoblast differentiation, Western blots indicated that nuclear levels of p53 were higher in TNF-treated myoblasts indicating that TNF does elevate p53. In contrast, in vivo studies in adult mdx mice showed that pifithrin-alpha significantly reduced myofibre necrosis that resulted from voluntary wheel running over 48 h. These results support the hypothesis that p53 plays some role in TNF-mediated necrosis of dystrophic muscle and present a potential new target for therapeutic interventions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.