calyculin-a and Cardiomyopathies

Patients with inherited dilated cardiomyopathy (DCM) often suffer from severe heart failure based on impaired cardiac contractility leading to increased morbidity and mortality. Integrin-linked kinase (ILK) as a part of the cardiac mechanical stretch sensor was found to be an essential genetic regulator of cardiac contractility. Integrin-linked kinase localizes to z-disks and costameres in vertebrate hearts and regulates the activity of the signaling molecule protein kinase B (PKB/Akt) by controlling its phosphorylation. Despite identification of several potential drug targets in the ILK signaling pathway, pharmacological treatment strategies to restore contractile function in ILK-dependent cardiomyopathies have not been established yet. In recent years, the zebrafish has emerged as a valuable experimental system to model human cardiomyopathies as well as a powerful tool for the straightforward high-throughput in vivo small compound screening of therapeutically active substances. Using the ILK deficient zebrafish heart failure mutant

Topics: Animals; Apoptosis; Cardiomyopathies; Disease Models, Animal; Enzyme Inhibitors; Humans; Marine Toxins; Myocardial Contraction; Okadaic Acid; Oxazoles; Phosphoric Monoester Hydrolases; Phosphorylation; Protein Serine-Threonine Kinases; Signal Transduction; Zebrafish; Zebrafish Proteins