Cardiomyocytes' prolonged IL-2 incubation induces enhancement in L-type Ca 2+ channels mediated by inhibitory-kappaB kinase/nuclear factor-kappaB signalling.

Autor: Mitrokhin V; Department of Fundamental and Applied Physiology, Russian National Research Medical University, Moscow, Russia., Gorbacheva L; Department of Fundamental and Applied Physiology, Russian National Research Medical University, Moscow, Russia., Vachrushev N; Department of Fundamental and Applied Physiology, Russian National Research Medical University, Moscow, Russia., Hadzi-Petrushev N; Faculty of Natural Sciences and Mathematics, Institute of Biology 'Saints Cyril and Methodius' University, Skopje, Macedonia., Kamkin A; Department of Fundamental and Applied Physiology, Russian National Research Medical University, Moscow, Russia., Mladenov M; Department of Fundamental and Applied Physiology, Russian National Research Medical University, Moscow, Russia.; Faculty of Natural Sciences and Mathematics, Institute of Biology 'Saints Cyril and Methodius' University, Skopje, Macedonia.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2021 Feb; Vol. 128 (2), pp. 234-240. Date of Electronic Publication: 2020 Oct 02.
DOI: 10.1111/bcpt.13491
Abstrakt: The main objective of this study was to determine the primary intracellular signalling pathway affected by prolonged (2 hours) incubation in interleukin-2 (IL-2). Based on the inflammatory nature of IL-2, priority was given to the involvement of inhibitory-kappaB kinase/nuclear factor-kappaB (IKK/NF-κB) signalling. All of the experiments were performed on freshly prepared cardiomyocytes isolated from rat left ventricles. After isolation, the whole-cell voltage-clamp recordings were performed on single cells. After 2 hours of incubation in IL-2, the current at 0 mV was approximately 100% higher than at the start of the incubation. ACHP, a highly specific kinase β inhibitor, in a concentration of 10 nmol/L, caused significant reduction in the I Ca,L . IL-2 (2 ng/mL) in the presence of 0.1 μmol/L IMD-0354 as a specific inhibitor of IKKβ, caused nearly no changes in the I Ca,L . IL-2 (3 ng/mL) induced a significant increase in phosphorylated NF-κB p65. The cardiomyocytes incubated in a Kraftbrühe solution containing IL-2 plus PDTC as a specific inhibitor of inducible nitric oxide synthase (iNOS) for 2 hours had a similar I Ca,L increase compared to the cells incubated only in IL-2. IL-2-induced enhancement in L-type Ca 2+ channels was mediated by IKK/NF-κB signalling, but not via iNOS-mRNA signalling.
(© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
Databáze: MEDLINE
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