Abstract
We show that mechanical separation of adherent rat primary hepatocytes after the monolayer-forming stage causes the induction of the oxidative stress genes HO-1 (haem oxygenase) and MnSOD (manganese superoxide dismutase). The procedures for enzymatically breaking up liver tissue structure and isolating hepatocytes do not cause HO-1 and MnSOD activation. Only after a 3-h incubation, during which hepatocytes form a monolayer on culture dishes, does the hydrodynamic shearing away of necrotic cells sticking to the monolayer surface activate these two genes. Analysis of this injury-response pathway shows that oxidative stress and mitochondrial dysfunction play a role, as activation can be repressed by antioxidants and by respiratory inhibitors. Recovery of the cells takes a further 24-h incubation during which HO-1 and MnSOD expression returns to basal levels.
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Received: 23 June 1998 / Accepted: 14 August 1998
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Pillar, T., Seitz, H. Oxidative stress response induced in rat primary hepatocyte monolayers by mechanical removal of adherent cells. Cell Tissue Res 295, 363–367 (1999). https://doi.org/10.1007/s004410051243
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DOI: https://doi.org/10.1007/s004410051243