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Involvement of microtubules in the tolerance of cardiomyocytes to cold ischemia-reperfusion

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Abstract

Before transplantation, the heart graft is preserved by the use of cold storage in order to limit ischemia-reperfusion stress. However, sustained exposure to low temperature may induce myocardial ultrastructural damage, particularly microtubules (MT) disruption. Previous data suggested that tubulin-binding agents are able to attenuate cold-induced cytoskeleton alterations. Thus, the aim of the present work was to study the influence of docetaxel (DX, a tubulin-binding taxane) on the effects of deep hypothermia (4°C) and of simulated cold ischemia-reperfusion on the MT network and oxidative stress of cardiomyocyte (CM) in monolayer cultures prepared from newborn rat ventricles. The MT network was explored by immunocytochemistry and Western-blotting, the cell stress by tetrazolium dye assay (MTT) and lactate dehydrogenase (LDH) release, and the superoxide production by the dihydroethidium probe (DHE). The MT assembly remained stable after 4 and 8 h of hypothermia. Tubulin acetylation was promoted in CM subjected to 4-h hypothermia. Low temperature reduced the mitochondrial function and increased the basal LDH release. The cold ischemia during 4 and 8 h preserved MT network. Docetaxel promoted MT polymerization and tubulin acetylation in basal and in cold conditions. This drug decreased the release of LDH induced by cold ischemia. Moreover, hypothermia (4 h) significantly raised the anion superoxide production. Docetaxel decreased this oxidative stress in the control CM and in CM submitted to 4 h of hypothermia. These data demonstrated that stabilizing MT with DX exerted a protective effect on CM subjected to hypothermia and to cold ischemia-reperfusion. Tubulin-ligands should be thus considered to improve the tolerance of the heart graft toward stressing conservative conditions.

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Acknowledgment

This work was supported by grants from the French Ministry of Research, Regional Council of Burgundy and French Federation of Cardiology. The authors are grateful to Dr Paul M. Walker for proof reading.

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Authors and Affiliations

  1. Laboratory of Experimental Cardiovascular Physiopathology and Pharmacology, IFR Santé-STIC, Institute of Cardiovascular Research, University Hospital Center, P.B. 77908, 21079, Dijon Cedex, France

    Lisa Devillard, David Vandroux, Cindy Tissier, Laure Dumont, Jessica Borgeot, Luc Rochette & Pierre Athias

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  1. Lisa Devillard
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  2. David Vandroux
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  3. Cindy Tissier
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  4. Laure Dumont
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  5. Jessica Borgeot
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  6. Luc Rochette
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  7. Pierre Athias
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Correspondence to Pierre Athias.

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Devillard, L., Vandroux, D., Tissier, C. et al. Involvement of microtubules in the tolerance of cardiomyocytes to cold ischemia-reperfusion. Mol Cell Biochem 307, 149–157 (2008). https://doi.org/10.1007/s11010-007-9594-3

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  • DOI: https://doi.org/10.1007/s11010-007-9594-3

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