BACKGROUND/AIMS: Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine. METHODS: Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species and reduced thio-group measurement, intracellular calcium measurement and mitochondrial calcium staining were performed in the study. RESULTS: Intracellular ATP was almost completely depleted within 12 hrs of hypothermic preservation in untreated human umbilical vein endothelial cells (HUVEC), while dopamine pre-treatment significantly delayed ATP depletion. 4 hrs after hypothermia a redox imbalance was observed in untreated cells, which increased with the duration of hypothermia. The redox imbalance was primarily caused by depletion of SH reduction equivalents and was significantly inhibited by dopamine. In addition, hypothermia-induced Ca(2+) influx and mitochondrial Ca(2+) accumulation were both prevented by dopamine. The protective effect of dopamine was abrogated by ionomycin and sodium azide and partly by oligomycin and CCCP. CONCLUSIONS: Our data demonstrated that loss of intracellular ATP, generation of a redox imbalance and accumulation of intracellular Ca(2+) underlie cold preservation injury. Dopamine improves the redox balance, prevents intracellular Ca(2+) accumulation and delays ATP depletion. Copyright 2008 S. Karger AG, Basel.
BACKGROUND/AIMS: Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine. METHODS: Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species and reduced thio-group measurement, intracellular calcium measurement and mitochondrial calcium staining were performed in the study. RESULTS: Intracellular ATP was almost completely depleted within 12 hrs of hypothermic preservation in untreated human umbilical vein endothelial cells (HUVEC), while dopamine pre-treatment significantly delayed ATP depletion. 4 hrs after hypothermia a redox imbalance was observed in untreated cells, which increased with the duration of hypothermia. The redox imbalance was primarily caused by depletion of SH reduction equivalents and was significantly inhibited by dopamine. In addition, hypothermia-induced Ca(2+) influx and mitochondrial Ca(2+) accumulation were both prevented by dopamine. The protective effect of dopamine was abrogated by ionomycin and sodium azide and partly by oligomycin and CCCP. CONCLUSIONS: Our data demonstrated that loss of intracellular ATP, generation of a redox imbalance and accumulation of intracellular Ca(2+) underlie cold preservation injury. Dopamine improves the redox balance, prevents intracellular Ca(2+) accumulation and delays ATP depletion. Copyright 2008 S. Karger AG, Basel.
Authors: Peter Schnuelle; Wilhelm H Schmitt; Christel Weiss; Antje Habicht; Lutz Renders; Martin Zeier; Felix Drüschler; Katharina Heller; Przemyslaw Pisarski; Bernhard Banas; Bernhard K Krämer; Matthias Jung; Kai Lopau; Christoph J Olbricht; Horst Weihprecht; Peter Schenker; Johan W De Fijter; Benito A Yard; Urs Benck Journal: Clin J Am Soc Nephrol Date: 2017-02-17 Impact factor: 8.237
Authors: Stephen F Vatner; Jie Zhang; Marko Oydanich; Tolga Berkman; Rotem Naftalovich; Dorothy E Vatner Journal: Ageing Res Rev Date: 2020-10-19 Impact factor: 10.895
Authors: Ralf M Lösel; Ulf Schnetzke; Paul T Brinkkoetter; Hui Song; Grietje Beck; Peter Schnuelle; Simone Höger; Martin Wehling; Benito A Yard Journal: PLoS One Date: 2010-03-16 Impact factor: 3.240