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Single Construct Suppression and Replacement Gene Therapy for the Treatment of All -, -, and -Mediated Arrhythmia Disorders.
Circ Arrhythm Electrophysiol
August 2024
Department of Molecular Pharmacology and Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory) (S.K.H., C.S.J.K., D.J.T., M. Gencarelli, K.E.T., M. Gluscevic, M.J.A.), Mayo Clinic, Rochester, MN.
Article Synopsis
- * Researchers developed a new gene therapy called CALM-SupRep, designed to suppress and replace malfunctioning genes associated with this syndrome using custom-made shRNAs.
- * The therapy successfully reduced elongated action potential durations in patient-derived heart cells, demonstrating potential as a viable treatment option for this condition.
Synergy of cAMP and calcium signaling pathways in CFTR regulation.
Proc Natl Acad Sci U S A
March 2017
Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada;
Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, leading to defective apical chloride transport. Patients also experience overactivation of inflammatory processes, including increased calcium signaling. Many investigations have described indirect effects of calcium signaling on CFTR or other calcium-activated chloride channels; here, we investigate the direct response of CFTR to calmodulin-mediated calcium signaling.
View Article and Find Full Text PDFOvarian carcinoma is the leading cause of death from gynecologic cancer in the developed world and is characterized by acquired chemoresistance leading to an overall 5-year survival rate of about 30 %. We previously showed that Bcl-xL and Mcl-1 cooperatively protect platinum-resistant ovarian cancer cells from apoptosis. Despite BH3-mimetics represent promising drugs to target Bcl-xL, anti-Mcl-1 strategies are still in pre-clinical studies and required new investigations.
View Article and Find Full Text PDFCalmodulin-mediated signal transduction pathways in Arabidopsis are fine-tuned by methylation.
Plant Cell
November 2013
Kentucky Tobacco Research and Development Center, College of Agriculture, University of Kentucky, Lexington, Kentucky 40546.
Calmodulin N-methyltransferase (CaM KMT) is an evolutionarily conserved enzyme in eukaryotes that transfers three methyl groups to a highly conserved lysyl residue at position 115 in calmodulin (CaM). We sought to elucidate whether the methylation status of CaM plays a role in CaM-mediated signaling pathways by gene expression analyses of CaM KMT and phenotypic characterization of Arabidopsis thaliana lines wherein CaM KMT was overexpressed (OX), partially silenced, or knocked out. CaM KMT was expressed in discreet spatial and tissue-specific patterns, most notably in root tips, floral buds, stamens, apical meristems, and germinating seeds.
View Article and Find Full Text PDFA bimodular mechanism of calcium control in eukaryotes.
Nature
November 2012
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Aarhus University, Gustav Wieds Vej 10c, DK-8000 Aarhus C, Denmark.
Calcium ions (Ca(2+)) have an important role as secondary messengers in numerous signal transduction processes, and cells invest much energy in controlling and maintaining a steep gradient between intracellular (∼0.1-micromolar) and extracellular (∼2-millimolar) Ca(2+) concentrations. Calmodulin-stimulated calcium pumps, which include the plasma-membrane Ca(2+)-ATPases (PMCAs), are key regulators of intracellular Ca(2+) in eukaryotes.
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