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DADLE induces a reversible hibernation-like state in HeLa cells

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Abstract

[d-Ala(2)-d-Leu(5)-Enkephalin] (DADLE) can induce hibernation when injected into ground squirrels in summer and is able to increase the survival time of explanted organs such as liver and lung. Since cell metabolism is a target of this peptide, we have treated HeLa cells with DADLE and investigated its possible effect on transcription and proliferation as well as the resumption of metabolic activity after treatment. The labelling for Pol I, Pol II and for splicing factors such as snRNPs and SC-35 decreased after treatment as did the nucleolar labelling for UBF. In treated cells, several spherical nuclear bodies were found to be labelled for hnRNPs. In parallel, the number of proliferating cells decreased after treatment with DADLE. After recovery, there was a gradual resumption of cell function: transcription and splicing factors had a distribution similar to that of controls; proliferation resumed; nuclear bodies, representing storage sites for RNPs, disappeared.

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Acknowledgements

The authors acknowledge the assistance of Dr. R. Lührmann (University of Marburg, Germany) for the generous gift of the anti-m3G cap, Dr. Claudia Alpini (IRCCS San Matteo Pavia, Italy) for the anti-Sm, Dr. Daniela Necchi for densitometric analysis of Western blots and Ms. Paola Veneroni for the cell cultures. We are also indebted to Dr. B. Carlhoun and M. Fornasiero for helpful discussions on the manuscript. This work was supported by MIUR (PRIN 2002) and Fondo di Ateneo per la Ricerca (FAR 2002).

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Authors and Affiliations

  1. Laboratorio di Biologia Cellulare e Neurobiologia, Dipartimento di Biologia Animale, Università di Pavia and Istituto di Genetica Molecolare del CNR, Piazza Botta 10, 27100, Pavia, Italy

    Lorella Vecchio, Cristiana Soldani, Maria Grazia Bottone, Carlo Pellicciari & Marco Biggiogera

  2. Istituto di Istologia ed Analisi di Laboratorio, University of Urbino “Carlo Bo”, 61029, Urbino, Italy

    Manuela Malatesta

  3. Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, 60637, USA

    Terence E. Martin

  4. Weis Center for Research, Geisinger Clinic, Pennsylvania, PA, 17822, USA

    Lawrence I. Rothblum

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  1. Lorella Vecchio
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  2. Cristiana Soldani
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  3. Maria Grazia Bottone
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  4. Manuela Malatesta
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  5. Terence E. Martin
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  6. Lawrence I. Rothblum
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  7. Carlo Pellicciari
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  8. Marco Biggiogera
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Correspondence to Marco Biggiogera.

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Vecchio, L., Soldani, C., Bottone, M.G. et al. DADLE induces a reversible hibernation-like state in HeLa cells. Histochem Cell Biol 125, 193–201 (2006). https://doi.org/10.1007/s00418-005-0085-x

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  • DOI: https://doi.org/10.1007/s00418-005-0085-x

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