Two mechanisms of calcium oscillations in adipocytes

Turovsky, Egor A.; Kaimachnikov, Nikolai P.; Turovskaya, M. V.; Berezhnov, Alexey V.; Дынник, В. В.; Зинченко, В. П.

doi:10.1134/s199074781106016x

Cited by 12 publications

(18 citation statements)

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“…However, these mechanisms may still be realized in adipocytes, where they are responsible for the generation of a so called “baseline” Ca 2+ oscillation observed in the presence of fetal bovine serum [50], [51]. It is known that activation of IP 3 R and PLC can be controlled by phosphorylation of the adaptor protein IRAG [79]–[82] and of the protein Regulators of G-protein Signaling (RGS) [83], [84] respectively by PKG.…”

Section: Resultsmentioning

confidence: 99%

“…Later on Woods et al [46] demonstrated Ca 2+ oscillations in non-excitable cells using single hepatocytes. Since that time various modes of Ca 2+ sparks, oscillations and waves and switching phenomena have been registered in hepatocytes [39], [40], [46], pancreatic β-cells [6], [47] and acini [37], [38], [48], smooth muscle cells [12], [16], [32]–[35], adipocytes [49]–[51], pituitary cells [52], endothelial cells [53]–[55], astrocytes [57], fibroblasts [58], interstitial cells [56], and T-cells [59] in the presence of ACh, cholecystokinin (CCK), bradykinin (BK), norepinephrine (NE), phenilephrine, histamine, c-type natriuretic peptide, ATP, 8-Br-cGMP, NO-donors, NAD, cADP ribose (cADPR), L-arginine, L-glutamate, bovine fetal serum, etc. The wide variety of specific mechanisms may underlie the observed dynamic regimes.…”

Section: Introductionmentioning

confidence: 99%

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Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide

et al. 2013

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PurposeThis study investigated possible mechanisms of autoregulation of Ca2+ signalling pathways in adipocytes responsible for Ca2+ and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP).MethodsFluorescent microscopy was used to detect changes in Ca2+ and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca2+-channels in Ca2+ signalling pathways.ResultsACh activating M3-muscarinic receptors and Gβγ protein dependent phosphatidylinositol 3 kinase induces Ca2+ and NO oscillations in adipocytes. At low concentrations of ACh which are insufficient to induce oscillations, NE or α1, α2-adrenergic agonists act by amplifying the effect of ACh to promote Ca2+ oscillations or switching phenomena. SNAP, 8-Br-cAMP, NAD and ANP may also produce similar set of dynamic regimes. These regimes arise from activation of the ryanodine receptor (RyR) with the implication of a long positive feedback loop (PFL): Ca2+→ NO→cGMP→cADPR→Ca2+, which determines periodic or steady operation of a short PFL based on Ca2+-induced Ca2+ release via RyR by generating cADPR, a coagonist of Ca2+ at the RyR. Interplay between these two loops may be responsible for the observed effects. Several other PFLs, based on activation of endothelial nitric oxide synthase or of protein kinase B by Ca2+-dependent kinases, may reinforce functioning of main PFL and enhance reliability. All observed regimes are independent of operation of the phospholipase C/Ca2+-signalling axis, which may be switched off due to negative feedback arising from phosphorylation of the inositol-3-phosphate receptor by protein kinase G.ConclusionsThis study presents a kinetic model of Ca2+-signalling system operating in adipocytes and integrating signals from various agonists, which describes it as multivariable multi feedback network with a family of nested positive feedback.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide

et al. 2013

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“…Realization of described regimes depends on the system's parameter values, that is, on the set of enzyme and channel activities and agonist affinities. All such regimes were observed experimentally in various types of cells [43][44][45][46][47][48][49][50][51] and were reproduced in mathematical models [52][53][54]. Apparently, all ranges of these dynamic regimes were observed for the first time on isolated hepatocytes [45].…”

Section: Two Ca 2+ -Dependent Signaling Systems and Rhythmic Processementioning

confidence: 86%

Feedback Control of Second Messengers Signaling Systems in White Adipose Tissue Adipocytes in Healthy State and Its Loss at Adiposity

Дынник¹,

Grishina²,

Сирота³

et al. 2018

Adipose Tissue

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Second messengers Ca 2+ , IP3, cAMP, NO, cGMP, and cADP ribose are incorporated as obligatory elements into multivariable Ca 2+-signaling system, which integrates incoming signals of hormones and neurotransmitters in white adipocytes. This cross-controlled system includes two robust generators (RGs) of rhythmic processes, involving phospholipase C-and NO-synthase-dependent signaling networks (PLC-RG and NOS-RG). Multi-loop positive feedback control of both RGs provides their robustness, multistability, signaling interplay, and extreme sensitivity to the alterations of incoming signals of acetylcholine, norepinephrine, insulin, cholecystokinin, atrial natriuretic peptide, bradykinin, and so on. Hypertrophy of cultured adipocytes and of mature cells, isolated from epididymal white adipose tissue (eWAT), results in the loss of rhythmicity and development of general hormonal signaling resistance. Preadipocytes isolated from eWAT of obese mice cannot grow and accumulate lipids in the media devoid of fatty acids. However, even low concentrations of palmitoylcarnitine in the media (1 μM) may result in drastic suppression of mRNA expressions of the proteins of Ca 2+-signaling system, especially of NOS-RG. Similar alterations of gene expression are observed in eWAT and liver at adiposity. All this may indicate on universal background pathogenic mechanisms. Treatment modalities, which may help to restore deregulation of Ca 2+-signaling system and corresponding tissues dysfunction, are discussed briefly.

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“…Ca 2+ ions are released from the ER to the cytosol through InsP 3 R and RyR. Because we found experimentally that RyR does not play a role in serum-induced oscillations in mesothelial cells similarly to other non-excitable cells [42], we focused on InsP 3 R. In our model, InsP 3 Rs are influenced both by c cyt and by c ER , however without an allosteric regulation between the two. InsP 3 Rs have Ca 2+ binding sites not only on the cytoplasmic side, but also on the luminal side [43].…”

Section: Building Up the Modelmentioning

confidence: 99%

Characterization and modeling of Ca2+ oscillations in mouse primary mesothelial cells

Pecze

Schwaller

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Brief changes in the cytosolic and intra-organellar Ca2+ concentration serve as specific signals for various physiological processes. In mesothelial cells lining the surface of internal organs and the walls of body cavities, a re-entry in the cell cycle (G0-G1 transition) evoked by serum re-administration induces long-lasting Ca2+ oscillations with a slowly decreasing frequency. Individual mesothelial cells show a wide range of different oscillatory patterns within a single, supposedly homogenous cell population. Changes in the cytoplasmic Ca2+ concentration (ccyt) show baseline oscillatory patterns i.e., discrete Ca2+ transients starting from a constant basal ccyt level. The ER Ca2+ concentration (cER) displays a sawtooth wave at a semi-depleted ER state; the minimum level is reached just briefly after the maximal value for ccyt. These oscillations depend on plasmalemmal Ca2+ influx and on the inositol trisphosphate concentration [InsP3]; the Ca2+ influx is a crucial determinant of the oscillation frequency. Partial blocking of SERCA pumps modifies the oscillation frequency in both directions, i.e. increasing it in some cells and lowering it in others. Current mathematical models for Ca2+ oscillations mostly fail to reproduce two experimentally observed phenomena: the broad range of interspike intervals and constant basal ccyt levels between two Ca2+ spikes. Here we developed a new model based on--and fitted to--Ca2+ recordings of ccyt and cER recorded in primary mouse mesothelial cells. The model allowed for explaining many features of experimentally observed Ca2+ oscillations. We consider this model to be suitable to simulate various types of InsP3 receptor-based baseline Ca2+ oscillations.

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Two mechanisms of calcium oscillations in adipocytes

Cited by 12 publications

References 17 publications

Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide

Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide

Feedback Control of Second Messengers Signaling Systems in White Adipose Tissue Adipocytes in Healthy State and Its Loss at Adiposity

Characterization and modeling of Ca2+ oscillations in mouse primary mesothelial cells

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