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- W2593441363 abstract "Redox changes can stimulate signal-transduction pathways, which are important for cell physio- and pathophysiology. Regarding cardiovascular diseases these include pathways involved in disease entities like ischemia or hypertrophy resulting in heart failure. Recent challenges to quantitatively describe defined redox changes include the application of newly developed redox biosensors. We generated αMHC driven cardiomyocyte-specific Grx1-roGFP2 sensor mice, in which the biosensor is expressed in the cytosol (cyto-Grx1-roGFP2) as well as targeted to the mitochondria (mito-Grx1-roGFP2). These mice now allow quantitative measurements of redox changes in both isolated intact cardiomyocytes and in the whole heart within the physiological context. The Grx1-roGFP2 biosensor is functionally expressed in these mice in both cytosol and mitochondria. H 2 O 2 and diamide induced an oxidative response in isolated cardiomyocytes, which were reverted by DTT treatment. Using Nernst equation the calculated glutathione redox potential (EGSH) for isolated resting cardiomyocytes in the mitochondria is -277.98 mV ± 0.66 mV and -275.98 mV ± 0.42 mV for two independent mouse lines. In the cytoplasm the calculated EGSH is -256.95 mV ± 0.79 mV and -256.31 mV ± 0.72 mV for two independent mouse lines respectively. Additionally, in the Langendorff perfused whole heart the redox potential in the mitochondria is calculated to be -275.27 ± 4.7 mV and in cytoplasm is -254.74 ± 6.2 mV. Isoprenaline stimulation of cardiomyocytes in the cyto-Grx1-roGFP2 shows an oscillation of the redox state whereas in mito-Grx1-roGFP2 mouse line isoprenaline stimulation shows an overall reduction in the mitochondria. Similar effects were observed with Angiotensin II stimulation as well in both the mouse lines. Current efforts aim to image changes in the redox potential simultaneously with the intracellular calcium levels." @default.
- W2593441363 created "2017-03-16" @default.
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- W2593441363 date "2016-11-01" @default.
- W2593441363 modified "2023-09-27" @default.
- W2593441363 title "Generation of a Cardiomyocyte-Specific Redox Sensor Mouse Line" @default.
- W2593441363 doi "https://doi.org/10.1016/j.freeradbiomed.2016.10.400" @default.
- W2593441363 hasPublicationYear "2016" @default.
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