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DMSO modulates the pathway of apoptosis triggering

Cellular & Molecular Biology Letters volume 16, pages 328–341 (2011)Cite this article

Abstract

We demonstrate here that distribution of caspase-9 influences the pathway of apoptosis triggering, since caspase-9 is activated efficiently only when it is distributed solely in the cytosol. Caspase-9 moves to the nuclei in a response to cell stress during isolation of primary hepatocytes; this is called preapoptotic cell stress response. The dimethyl sulfoxide (DMSO) treatment cannot prevent the migration of caspase-9 into the nuclei when it is added to primary hepatocytes immediately after isolation; however, it can trigger redistribution of caspase-9 from the nuclei into the cytosol when added 1 day post-isolation. This redistribution is temporary, since caspase-9 returns to the nuclei within 48 hours of DMSO treatment. Thereafter, some caspase-9 is retained in the nuclei of DMSO-treated hepatocytes for longer than in the nuclei of untreated hepatocytes. By measuring caspase activities, we demonstrate that the addition of DMSO to cell culture medium can temporarily normalize the susceptibility of hepatocytes for apoptosis triggering through the intrinsic pathway. DMSO contributes also to the prolonged pathway inactivation, i.e., by extending preapoptotic cell stress response. We propose that DMSO extends the survival of primary hepatocytes by modulating preapoptotic cell stress response, which could be exploited for extending the lifespan of other primary cell cultures.

Abbreviations

CHO:

Chinese hamster ovary

DMSO:

dimethyl sulfoxide

FCS:

fetal calf serum

MTT:

2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide

STS:

staurosporine

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Authors and Affiliations

  1. Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, SI-1000, Ljubljana, Slovenia

    Blaž Banič, Damijan Nipič, Dušan Šuput & Irina Milisav

  2. Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia

    Irina Milisav

Authors
  1. Blaž Banič
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  2. Damijan Nipič
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  3. Dušan Šuput
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  4. Irina Milisav
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Correspondence to Irina Milisav.

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These authors contributed equally to this work

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Banič, B., Nipič, D., Šuput, D. et al. DMSO modulates the pathway of apoptosis triggering. Cell Mol Biol Lett 16, 328–341 (2011). https://doi.org/10.2478/s11658-011-0007-y

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  • DOI: https://doi.org/10.2478/s11658-011-0007-y

Key words

Cellular & Molecular Biology Letters

ISSN: 1689-1392

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