FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.2.1

Title of the proposal

Endogenous protection-related, Ca²⁺-involving signalling between subcellular membrane systems of the myocardium. Response to diverse pathological stimuli.

Institute

Slovak Academy of Sciences, Institute for Heart Research
Dubravska cesta 9, 849 33 Bratislava, Slovak Republic

Contact

Research subject for a potential FP6 project

In recent years we have shown: a) that pathological impulses such as ischemia, free radicals, calcium overload, diabetes etc., induce besides cardiac damage also endogenous protective mechanisms in the myocardium; b) that measures taken for protection of the heart against the above damages may also prevent the development of endogenous protective mechanisms the heart. The present project is designed to distinguish the endogenous protective mechanisms from other alterations, study their mechanisms, genomic control and functional manifestation with the aim for finding modes to their support and minimalize the risks caused by their treatment-induced depression. This may contribute to innovation of cardioprotective treatment and to development of new drugs. These goals are followed by study of functional properties of heart and on molecular level of the heart sarcolemmal and mitochondrial membranes such as of the ion transporting pumps, channels and receptors, oxidative phosphorylation, electron-oxygen and transmembrane energy transport (mitochondrial contact sites formation), in conjunction with membrane fluidity and potential. Special interest is devoted to elucidation of character and mechanisms of signals (partricularly by Ca²⁺) providing functional coupling between the systems investigated. Normal and transgenic (S100A1 deficient, etc.) animals will be used in the experiments.

Recent international cooperation of the research team

Heart Center, Department of Medicine, Rigshospitalet Copenhagen, Copenhagen, Danmark;
Mack Planck Institute, Department of Experimental Cardiology, Bad Nauheim, Germany;
Institute of Physiology, University of Leipzig, Leipzig, Germany;
Department of Pharmacology and Pharmacotherapy, University of Szeged, Faculty of Medicine, Szeged, Hungary;
Institute of Physiology, Academy of Sciences of the Czech Republic and Centre forCardiovascular Research, Prague, Czech Republic;

Proposer´s relevant publications related to the research subject

-Ziegelhoffer A. at all.: Mechanisms that may be involved in calcium tolerance of the diabetic heart. Molecular and Cellular Biochemistry, 1997, 176, 191-198.
Ziegelhoffer-Mihalovicova B., Okruhlicova L., Tribulova N., Ravingerova T., Volkovova K., Sebokova J., Ziegelhoffer A.: Mitochondrial contact sites detected by creatine phosphokinase activity in the hearts of normal and diabetic rats. Is mitochondrial contact site formation a calcium dependent process? General Physiology and Biophysics, 1997, 16, 329-338.
- Ziegelhoffer A. at all.: Prevention of processes coupled with free radical formation prevents also the develoment of calcium resistance in the diabetic heart. Life Sciences, 1999, 65, 1999-2001.
-Ziegelhoffer A. at all.: Low level of sarcolemmal phosphatidylinositol 4,5-bisphosphate in cardiomyopathic hamster (UM-X7.1) heart. Cardiovascular Research, 2001, 49, 118-126.
-Ravingerova T., Neckar J., Kolar F., Stetka R., Volkovova K., Ziegelhoffer A.. Styk J.: Ventricular arrhythmias following coronary artery occlusion in rats: is the diabetic heart less or more sensitive to ischemia? Basic Research in Cardiology, 2001, 96, 160-168.