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[Animal in vivo model of arrhythmia for genes target identification for 5-amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one].
- Source :
-
Bioorganicheskaia khimiia [Bioorg Khim] 2011 Nov-Dec; Vol. 37 (6), pp. 821-9. - Publication Year :
- 2011
-
Abstract
- The goal of the current work is to study the molecular mechanisms underlay the action of 5- amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one (P-11) with combined antiarrhythmic, nootropic, anti-inflammatory and anaesthetic activities. The aconitine-induced experimental rat model of cardiac arrhythmia has been used in our study. Aconitine was administered once intravenously in a dose 50 microg/kg whereas experimental animal group received P-11 in a dose 0.3 mg/kg (the compound was injected intravenously 2 min before acute aconitine treatment). Expression macroarray (Atlas Rat cDNA Expression Array, #7738-1; BD Biosciences) was used to identify the target genes for P-11 compound. Comparative analysis of changes in the status of expression of genes in the heart of rats induced by P-11 against the simulated in vivo arrhythmia identified 16 genes that reproducibly alter the level of expression.These genes encode the extracellular matrix proteins (glypican 1, Gpc1; tissue inhibitor of metalloproteinase 2, 3, Timp2, Timp 3); intracellular signaling molecules (rho GTPase activating protein 7, Dlc1; protein tyrosine phosphatase 4a1, Ptp4a1; phosphodiesterase 4D, PDE4D; PI3-kinase regulatory subunit alpha, PIK3R1; guanine nucleotide binding protein alpha 12, Gna12) and protein of intermediate junctions (junction plakoglobin, Jup), proteins involved in glycolysis (phosphofructokinase I, Pfk1) and hemostasis (tissue plasminogen activator, Plat), plasma membrane transporters (Solute carrier family 16, member 1, Slc16a1; ATPase, Na+/K+ transporting, Atp1a), and ets. (c-fos protooncogene, c-fos; telomerase protein component 1, tlp; Annexin 1, anxa 1). Thus, the data about the selective effect of P-11 on genes whose products are involved in the aritmogenesys mechanisms, allow us to consider this compound as a promising means of pathogenetically oriented pharmacotherapy of cardiac arrhythmias.
- Subjects :
- Aconitine administration & dosage
Animals
Anti-Arrhythmia Agents chemical synthesis
Arrhythmias, Cardiac genetics
Aza Compounds chemistry
Aza Compounds metabolism
Disease Models, Animal
Extracellular Matrix Proteins genetics
Extracellular Matrix Proteins metabolism
Intracellular Signaling Peptides and Proteins genetics
Intracellular Signaling Peptides and Proteins metabolism
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
Oligonucleotide Array Sequence Analysis
Rats
Anti-Arrhythmia Agents pharmacology
Arrhythmias, Cardiac drug therapy
Gene Expression drug effects
Subjects
Details
- Language :
- Russian
- ISSN :
- 0132-3423
- Volume :
- 37
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioorganicheskaia khimiia
- Publication Type :
- Academic Journal
- Accession number :
- 22497081
- Full Text :
- https://doi.org/10.1134/s1068162011060148