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Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver

Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver

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Prüfsumme: MD5:1cf8e9ac302e0cc196cd2bd145c63446

PLOCK, Jan, Steffen FRESE, Adrian KEOGH, Sonja BISCH-KNADEN, Erick AYUNI, Nadia CORAZZA, Christian WEIKERT, Stephan JAKOB, Dominique ERNI, Jean-Francois DUFOUR, Thomas BRUNNER, Daniel CANDINAS, Deborah STROKA, 2007. Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver. In: Journal of Hepatology. 47(4), pp. 538-545. ISSN 0168-8278. Available under: doi: 10.1016/j.jhep.2007.04.016

@article{Plock2007-10Activ-14273, title={Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver}, year={2007}, doi={10.1016/j.jhep.2007.04.016}, number={4}, volume={47}, issn={0168-8278}, journal={Journal of Hepatology}, pages={538--545}, author={Plock, Jan and Frese, Steffen and Keogh, Adrian and Bisch-Knaden, Sonja and Ayuni, Erick and Corazza, Nadia and Weikert, Christian and Jakob, Stephan and Erni, Dominique and Dufour, Jean-Francois and Brunner, Thomas and Candinas, Daniel and Stroka, Deborah} }

Keogh, Adrian Erni, Dominique Candinas, Daniel Erni, Dominique Dufour, Jean-Francois Frese, Steffen Ayuni, Erick Jakob, Stephan Stroka, Deborah Candinas, Daniel 2011-10-19T14:37:32Z Background/Aims:<br />We investigated the molecular response of a non-ischemic hypoxic stress in the liver, in particular, to distinguish its hepatoprotective potential.<br />Methods:<br />The livers of mice were subjected to non-ischemic hypoxia by clamping the hepatic-artery (HA) for 2h while maintaining portal circulation. Hypoxia was defined by a decrease in oxygen saturation, the activation of hypoxia-inducible factor (HIF)-1 and the mRNA up-regulation of responsive genes. To demonstrate that the molecular response to hypoxia may in part be hepatoprotective, pre-conditioned animals were injected with an antibody against Fas (Jo2) to induce acute liver failure. Hepatocyte apoptosis was monitored by caspase-3 activity, cleavage of lamin A and animal survival.<br />Results:<br />Clamping the HA induced a hypoxic stress in the liver in the absence of severe metabolic distress or tissue damage. The hypoxic stimulus was sufficient to activate the HIF-1 signalling pathway and up-regulate hepatoprotective genes. Pre-conditioning the liver with hypoxia was able to delay the onset of Fas-mediated apoptosis and prolong animal survival.<br />Conclusions:<br />Our data reveal that hepatic cells can sense and respond to a decrease in tissue oxygenation, and furthermore, that activation of hypoxia-inducible signalling pathways function in part to promote liver cell survival. Brunner, Thomas Stroka, Deborah Bisch-Knaden, Sonja Ayuni, Erick Dufour, Jean-Francois 2007-10 Corazza, Nadia Brunner, Thomas Keogh, Adrian Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver Plock, Jan deposit-license Corazza, Nadia Weikert, Christian Weikert, Christian eng Plock, Jan Journal of Hepatology ; 47 (2007), 4. - pp. 538-545 Frese, Steffen Jakob, Stephan 2011-10-19T14:37:32Z Bisch-Knaden, Sonja

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