Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Oberhofer, M; Tian, Q; Ruppenthal, S; Wegener, S; Reil, JC; Körbel, C; Hammer, K; Menger, M; Neuberger, HR; Kaestner, L; Lipp, P.
Calcium dysregulation in ventricular myocytes from mice expressing constitutively active Rac1.
Cell Calcium. 2013; 54(1):26-36
Doi: 10.1016/j.ceca.2013.03.006
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Hammer Karin Petra
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- Abstract:
- Increased Rac1 activity and its concomitant elevation of reactive oxygen species (ROS) levels is believed to be involved in the development of cardiac diseases such as hypertrophy and arrhythmia. To study the effects of activated Rac1 on the properties of isolated ventricular myocytes we used a transgenic mouse model (RacET) expressing constitutively active Rac1. Concurrent with dilated cardiomyopathy global Ca(2+) handling as well as single cell contractility was substantially decreased. Cellular ROS levels were assessed with two independent assays and unexpectedly depicted decreased ROS production in RacET that was uncoupled from hormonal stimulation. Western blot analysis illustrated a massive increase in cellular Rac1 activity concomitant with a reduction in NADPH-oxidase activity. Analysis of the Ca(2+) current, the ryanodine receptor and fractional Ca(2+) release uncovered defective excitation-contraction (ec) coupling and a substantial increase in sarcoplasmic reticulum Ca(2+) leak together with a larger Ca(2+) spark amplitude and frequency. We conclude that Rac1 activity plays an important role for cardiac diseases but can be uncoupled from NADPH-oxidase activity. Rac1-mediated partial uncoupling of the ec-coupling machinery results in a ROS-independent disarrayed cellular Ca(2+) handling, contractility and impaired cardiac function.
- Find related publications in this database (using NLM MeSH Indexing)
- Action Potentials - physiology
- Animals -
- Calcium - metabolism
- Calcium Channels, L-Type - physiology
- Cells, Cultured -
- Heart Ventricles - cytology
- Male -
- Membrane Glycoproteins - metabolism
- Mice -
- Mice, Transgenic -
- Models, Animal -
- Myocytes, Cardiac - cytology
- NADPH Oxidase - metabolism
- Neuropeptides - genetics
- Reactive Oxygen Species - metabolism
- Sarcoplasmic Reticulum - metabolism
- rac1 GTP-Binding Protein - genetics
- Find related publications in this database (Keywords)
- NADPH oxidase
- Reactive oxygen species
- Rac
- Cardiomyopathy
- Excitation contraction coupling
- Calcium handling
- Calcium spark