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Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

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Abstract

The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.

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Acknowledgements

This work was supported by grant SROP-4.2.2/B-10/1-2010-0029. The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pécs, Hungary.

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Authors and Affiliations

  1. Department of Medical Biology, Medical School, University of Pécs, Szigeti út 12, Pécs, 7624, Hungary

    R. Schipp, J. Varga, J. Bátor, M. Vecsernyés, Z. Árvai, M. Pap & József Szeberényi

  2. Signal Transduction Research Group, Szentágothai Research Centre, Ifjúság útja 20, Pécs, 7624, Hungary

    R. Schipp, J. Varga, J. Bátor, M. Vecsernyés, Z. Árvai, M. Pap & József Szeberényi

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Schipp, R., Varga, J., Bátor, J. et al. Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells. Mol Cell Biochem 434, 41–50 (2017). https://doi.org/10.1007/s11010-017-3035-8

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