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Volume 16, Issue 2


DMSO modulates the pathway of apoptosis triggering

Blaž Banič / Damijan Nipič / Dušan Šuput / Irina Milisav
Published Online: 2011-03-26 | DOI: https://doi.org/10.2478/s11658-011-0007-y


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.

Keywords: Apoptosis; Preapoptotic cell stress response; DMSO; Hepatocytes; Caspase-9; Intrinsic pathway

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About the article

Published Online: 2011-03-26

Published in Print: 2011-06-01

Citation Information: Cellular and Molecular Biology Letters, Volume 16, Issue 2, Pages 328–341, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-011-0007-y.

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© 2011 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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