title: [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].
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.
authors.forename: Iu V
authors.initials: IuV
authors.lastname: Vakhitova
authors.forename: E I
authors.initials: EI
authors.lastname: Antipina
authors.forename: R S
authors.initials: RS
authors.lastname: Yamidanov
authors.forename: R Iu
authors.initials: RIu
authors.lastname: Khisamutdinova
authors.forename: F S
authors.initials: FS
authors.lastname: Zarudiĭ
authors.forename: N Zh
authors.initials: NZh
authors.lastname: Baschenko
authors.forename: V A
authors.initials: VA
authors.lastname: Dokichev
authors.forename: Iu V
authors.initials: IuV
authors.lastname: Tomilov
authors.forename: O M
authors.initials: OM
authors.lastname: Nefedov
mesh_terms: D000157:Aconitine / Q000008:administration & dosage; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000235:genetics; D001372:Aza Compounds / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats
chemical_list: C572464:5-amino-exo-3-azatricyclo(5.2.1.0(2,6))decan-4-one; D000889:Anti-Arrhythmia Agents; D001372:Aza Compounds; D016326:Extracellular Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D000157:Aconitine