8 results on '"Koltsova, A. V."'
Search Results
2. HCO3 dependent impact of Na+,K+, 2Cl cotransport in vascular smooth muscle excitation-contraction coupling
- Author
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Koltsova, Svetlana V., Luneva, Oksana G., Lavoie, Julie, Tremblay, Johanne, Maksimov, Georgy V., Hamet, Pavel, Orlov, Serguei, and Université de Montréal. Faculté de médecine. Département de médecine
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Bicarbonate ,2Cl ,Contraction ,Vascular smooth muscle cells ,Cotransport ,Na+ ,K+ - Abstract
In smooth muscles, inhibition of Na(+),K(+),2Cl(-) cotransport (NKCC) by bumetanide decreased intracellular Cl(-) content ([Cl(-)](i)) and suppressed the contractions triggered by diverse stimuli. This study examines whether or not bicarbonate, a regulator of several Cl(-) transporters, affects the impact of NKCC in excitation-contraction coupling. Addition of 25 mM NaHCO(3) attenuated the inhibitory action of bumetanide on mesenteric artery contractions evoked by 30 mM KCl and phenylephrine (PE) by 5 and 3-fold, respectively. In cultured vascular smooth muscle cells, NaHCO(3) almost completely abolished inhibitory actions of bumetanide on transient depolarization and [Ca(2+)](i) elevation triggered by PE. In bicarbonate-free medium, bumetanide decreased [Cl(-)](i) by approximately 15%; this effect was almost totally abrogated by NaHCO(3). The addition of NaHCO(3) resulted in 2-fold inhibition of NKCC activity and 3-fold attenuation of [Cl(-)](i). These data strongly suggest that extracellular HCO(3)(-) diminishes the NKCC-sensitive component of excitation-contraction coupling via suppression of this carrier.
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- 2009
3. Transcriptomic Changes Triggered by Hypoxia: Evidence for HIF-1α -Independent, [Na+]i/[K+]i-Mediated, Excitation-Transcription Coupling.
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Koltsova, Svetlana V., Shilov, Boris, Birulina, Julia G., Akimova, Olga A., Haloui, Mounsif, Kapilevich, Leonid V., Gusakova, Svetlana V., Tremblay, Johanne, Hamet, Pavel, and Orlov, Sergei N.
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HYPOXIA-inducible factor 1 , *GENETIC transcription , *CELLULAR signal transduction , *GENE expression , *REPERFUSION - Abstract
This study examines the relative impact of canonical hypoxia-inducible factor-1alpha- (HIF-1α and Na+i/K+i-mediated signaling on transcriptomic changes evoked by hypoxia and glucose deprivation. Incubation of RASMC in ischemic conditions resulted in ∼3-fold elevation of [Na+]i and 2-fold reduction of [K+]i. Using global gene expression profiling we found that Na+,K+-ATPase inhibition by ouabain or K+-free medium in rat aortic vascular smooth muscle cells (RASMC) led to the differential expression of dozens of genes whose altered expression was previously detected in cells subjected to hypoxia and ischemia/reperfusion. For further investigations, we selected Cyp1a1, Fos, Atf3, Klf10, Ptgs2, Nr4a1, Per2 and Hes1, i.e. genes possessing the highest increments of expression under sustained Na+,K+-ATPase inhibition and whose implication in the pathogenesis of hypoxia was proved in previous studies. In ouabain-treated RASMC, low-Na+, high-K+ medium abolished amplification of the [Na+]i/[K+]i ratio as well as the increased expression of all tested genes. In cells subjected to hypoxia and glucose deprivation, dissipation of the transmembrane gradient of Na+ and K+ completely eliminated increment of Fos, Atf3, Ptgs2 and Per2 mRNAs and sharply diminished augmentation expression of Klf10, Edn1, Nr4a1 and Hes1. In contrast to low-Na+, high-K+ medium, RASMC transfection with Hif-1a siRNA attenuated increments of Vegfa, Edn1, Klf10 and Nr4a1 mRNAs triggered by hypoxia but did not impact Fos, Atf3, Ptgs2 and Per2 expression. Thus, our investigation demonstrates, for the first time, that Na+i/K+i-mediated, Hif-1α- -independent excitation-transcription coupling contributes to transcriptomic changes evoked in RASMC by hypoxia and glucose deprivation. [ABSTRACT FROM AUTHOR]
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- 2014
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4. Increased Renal Epithelial Na Channel Expression and Activity Correlate With Elevation of Blood Pressure in Spontaneously Hypertensive Rats.
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Haloui, Mounsif, Tremblay, Johanne, Seda, Ondrej, Koltsova, Svetlana V., Maksimov, Georgy V., Orlov, Sergei N., and Hamet, Pavel
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- 2013
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5. Ubiquitous [Na+]i/[K+]i-Sensitive Transcriptome in Mammalian Cells: Evidence for Ca2+i-Independent Excitation-Transcription Coupling.
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Koltsova, Svetlana V., Trushina, Yulia, Haloui, Mounsif, Akimova, Olga A., Tremblay, Johanne, Hamet, Pavel, and Orlov, Sergei N.
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ISCHEMIA , *GENETIC transcription , *BLOOD circulation disorders , *PHOSPHOPROTEIN phosphatases , *GENETIC regulation , *MUSCLE cells - Abstract
Stimulus-dependent elevation of intracellular Ca2+ ([Ca2+]i) affects the expression of numerous genes - a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na+]i trigger c-Fos expression via a novel Ca2+i-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na+]i/[K+]i-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na+]i and reduce [K+]i, cells were treated for 3 hrs with the Na+,K+-ATPase inhibitor ouabain or placed for the same time in the K+- free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p<0.0001; R2.0.62). Among these Na+ i/K+ i-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca2+]i, we performed identical experiments in Ca2+-free media supplemented with extracellular and intracellular Ca2+ chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell-type specific Na+i/K+i-sensitive genes. Among the ubiquitous Na+i/K+i-sensitive genes whose expression was regulated independently of the presence of Ca2+ chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca2+-depleted cells. Overall, our findings indicate that Ca2+i-independent mechanisms of excitation-transcription coupling are involved in transcriptomic alterations triggered by elevation of the [Na+]i/[K+]i ratio. There results likely have profound implications for normal and pathological regulation of mammalian cells, including sustained excitation of neuronal cells, intensive exercise and ischemia-triggered disorders. [ABSTRACT FROM AUTHOR]
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- 2012
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6. Activation of P2Y receptors causes strong and persistent shrinkage of C11-MDCK renal epithelial cells.
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Koltsova, Svetlana V., Platonova, Alexandra, Maksimov, Georgy V., Mongin, Alexander A., Grygorczyk, Ryszard, and Orlov, Sergei N.
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CELL physiology , *CELL receptors , *EPITHELIAL cells , *PROTEIN kinase C , *CELL lines , *ION channels , *PURINERGIC receptors - Abstract
Purinergic receptors activate diverse signaling cascades and regulate the activity of cell volume-sensitive ion transporters. However, the effects of ATP and other agonists of P2 receptors on cell volume dynamics are only scarcely studied. In the present work, we used the recently developed dual-image surface reconstruction technique to explore the influence of purinergic agonists on cell volume in the C11-Madin-Darby canine kidney cell line resembling intercalated cells from kidney collecting ducts. Unexpectedly, we found that ATP and UTP triggered very robust (55-60%) cell shrinkage that lasted up to 2 h after agonist washout. Purinergic regulation of cell volume required increases in intracellular Ca2+ and could be partially mimicked by the Ca2+-ionophore ionomycin or activation of protein kinase C by 4β-phorbol 12-myristate 13-acetate. Cell shrinkage was accompanied by strong reductions in intracellular K+ and Cl- content measured using steady-state 86Rb+ and 36Cl- distribution. Both shrinkage and ion efflux in ATP-treated cells were prevented by the anion channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and by the BKCa channel inhibitors charybdotoxin, iberiotoxin, and paxilline. To evaluate the significance of cell-volume changes in purinergic signaling, we measured the impact of ATP on the expression of the immediate-early gene c-Fos. Thirty-minute treatment with ATP increased c-Fos immunoreactivity by approximately fivefold, an effect that was strongly inhibited by charybdotoxin and completely prevented by NPPB. Overall, our findings suggest that ATP-induced cell-volume changes are partially responsible for the physiological actions of purinergic agonists. [ABSTRACT FROM AUTHOR]
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- 2011
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7. Molecular origin of Na+/Li+ exchanger: Evidence against the involvement of major cloned erythrocyte transporters
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Koltsova, Svetlana V., Trushina, Yulia A., Akimova, Olga A., Hamet, Pavel, and Orlov, Sergei N.
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MOLECULAR biology , *SODIUM channels , *LITHIUM ions , *ION exchange (Chemistry) , *ERYTHROCYTES , *BIOLOGICAL transport - Abstract
Abstract: Numerous studies have demonstrated heightened Na+/Li+ countertransport (NLCT) activity in erythrocytes of patients with essential hypertension or diabetic nephropathy. The same carrier also contributes to the therapeutic action of lithium salt, widely used in the treatment of psychiatric disorders. However, the molecular origin of NLCT remains unknown. This study examined the role of major ion transporters in NLCT by comparative analysis of its activity and that of ion transporters providing inwardly directed 86Rb, 22Na and 32P fluxes. NLCT was below the detection limit in rat erythrocytes and ∼50-fold higher in rabbits compared to humans. Unlike NLCT, the activities of Na+,K+-ATPase, Na+,K+,2Cl− cotransporter and anion exchanger were somewhat similar in the erythrocytes of these species, whereas Na+,Pi cotransport was in 1:2:6 proportion in rats, humans and rabbits, respectively. Loading of erythrocytes with Li+ for NLCT measurement did not affect the activity of Na+,Pi cotransporter. Keeping in mind that NLCT is much higher in rabbits vs humans and rats, we compared the set of membrane proteins in these species using 2-dimensional gel electrophoresis. This approach revealed 174 common spots, whereas 132 proteins were detected only in human and rabbit erythrocyte membranes. Among these proteins, we found 17 spots whose expression was higher by more than 5-fold in rabbit compared to human erythrocytes. Thus, our results argue against the involvement of major ion transporters in NLCT. They also show that comparative proteomics is a potent tool to identify the molecular origin of this carrier. [Copyright &y& Elsevier]
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- 2011
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8. Time- and dose dependent actions of cardiotonic steroids on transcriptome and intracellular content of Na+ and K+: a comparative analysis.
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Klimanova, Elizaveta A., Tverskoi, Artem M., Koltsova, Svetlana V., Sidorenko, Svetlana V., Lopina, Olga D., Tremblay, Johanne, Hamet, Pavel, Kapilevich, Leonid V., and Orlov, Sergei N.
- Abstract
Recent studies demonstrated that in addition to Na
+ ,K+ -ATPase inhibition cardiotonic steroids (CTSs) affect diverse intracellular signaling pathways. This study examines the relative impact of [Na+ ]i /[K+ ]i -mediated and -independent signaling in transcriptomic changes triggered by the endogenous CTSs ouabain and marinobufagenin (MBG) in human umbilical vein endothelial cells (HUVEC). We noted that prolongation of incubation increased the apparent affinity for ouabain estimated by the loss of [K+ ]i and gain of [Na+ ]i . Six hour exposure of HUVEC to 100 and 3,000 nM ouabain resulted in elevation of the [Na+ ]i /[K+ ]i ratio by ~15 and 80-fold and differential expression of 258 and 2185 transcripts, respectively. Neither [Na+ ]i /[K+ ]i ratio nor transcriptome were affected by 6-h incubation with 30 nM ouabain. The 96-h incubation with 3 nM ouabain or 30 nM MBG elevated the [Na+ ]i /[K+ ]i ratio by ~14 and 3-fold and led to differential expression of 880 and 484 transcripts, respectively. These parameters were not changed after 96-h incubation with 1 nM ouabain or 10 nM MBG. Thus, our results demonstrate that elevation of the [Na+ ]i /[K+ ]i ratio is an obligatory step for transcriptomic changes evoked by CTS in HUVEC. The molecular origin of upstream [Na+ ]i /[K+ ]i sensors involved in transcription regulation should be identified in forthcoming studies. [ABSTRACT FROM AUTHOR]- Published
- 2017
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