Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells death

2009 ◽  
Vol 297 (5) ◽  
pp. C1133-C1145 ◽  
Author(s):  
Ludivine Mondin ◽  
Haouaria Balghi ◽  
Bruno Constantin ◽  
Christian Cognard ◽  
Stéphane Sebille
Keyword(s):  
Cell Death ◽  
Calcium Signaling ◽  
Calcium Release ◽  
Receptor Expression ◽  
Type I ◽  
Ip3 Receptors ◽  
Inositol 1,4,5 Trisphosphate ◽  
Interesting Approach ◽  
Long Time ◽  
Short Time

Evidence for a modulatory effect of cyclosporin A (CsA) on calcium signaling and cell survival in dystrophin-deficient cells is presented. Our previous works strongly supported the hypothesis of an overactivation of Ca2+ release via inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in dystrophin-deficient cells, both during membrane depolarization and at rest, through spontaneous Ca2+ release events. Forced expression of mini-dystrophin in these cells contributed, during stimulation and in resting condition, to the recovery of a controlled calcium homeostasis. In the present work, we demonstrate that CsA exposure displayed a dual-modulator effect on calcium signaling in dystrophin-deficient cells. Short-time incubation induced a decrease of IP3-dependent calcium release, leading to patterns of release similar to those observed in myotubes expressing mini-dystrophin, whereas long-time incubation reduced the expression of the type I of IP3 receptors (IP3R-1) RNA levels. Moreover, both IP3R-1 knockdown and blockade through 2-aminoethoxydiphenyle borate or CsA induced improved survival of dystrophin-deficient myotubes, demonstrating the cell death dependence on the IP3-dependent calcium signaling as well as the protective effect of CsA. Inhibition of the IP3 pathway could be a very interesting approach for reducing the natural cell death of dystrophin-deficient cells in development.

scholarly journals Mini-dystrophin Expression Down-regulates IP3-mediated Calcium Release Events in Resting Dystrophin-deficient Muscle Cells

2006 ◽  
Vol 128 (2) ◽  
pp. 219-230 ◽  
Author(s):  
Haouaria Balghi ◽  
Stéphane Sebille ◽  
Ludivine Mondin ◽  
Anne Cantereau ◽  
Bruno Constantin ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Release Site ◽  
Cell Types ◽  
Ip3 Receptors ◽  
Calcium Signaling Pathway ◽  
Gi Protein

We present here evidence for the enhancement, at rest, of an inositol 1,4,5-trisphosphate (IP3)–mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(−)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, the number of sites discharging calcium (release site density [RSD]) was quantified and found more elevated in SolC1(−) than in SolD(+) myotubes. Variations of membrane potential had no significant effect on this difference, and higher resting [Ca2+]i in SolC1(−) (Marchand, E., B. Constantin, H. Balghi, M.C. Claudepierre, A. Cantereau, C. Magaud, A. Mouzou, G. Raymond, S. Braun, and C. Cognard. 2004. Exp. Cell Res. 297:363–379) cannot explain alone higher RSD. The exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) and phospholipase C inhibitor (U73122) significantly reduced RSD in both cell types but with a stronger effect in dystrophin-deficient SolC1(−) myotubes. Immunocytochemistry allowed us to localize ryanodine receptors (RyRs) as well as IP3 receptors (IP3Rs), IP3R-1 and IP3R-2 isoforms, indicating the presence of both RyRs-dependent and IP3-dependent release systems in both cells. We previously reported evidence for the enhancement, through a Gi protein, of the IP3-mediated calcium signaling pathway in SolC1(−) as compared to SolD(+) myotubes during a high K+ stimulation (Balghi, H., S. Sebille, B. Constantin, S. Patri, V. Thoreau, L. Mondin, E. Mok, A. Kitzis, G. Raymond, and C. Cognard. 2006. J. Gen. Physiol. 127:171–182). Here we show that, at rest, these regulation mechanisms are also involved in the modulation of calcium release activities. The enhancement of resting release activity may participate in the calcium overload observed in dystrophin-deficient myotubes, and our findings support the hypothesis of the regulatory role of mini-dystrophin on intracellular signaling.

Nitric oxide inhibits calcium release from sarcoplasmic reticulum of porcine tracheal smooth muscle cells

1997 ◽  
Vol 272 (1) ◽  
pp. L1-L7 ◽  
Author(s):  
M. S. Kannan ◽  
Y. S. Prakash ◽  
D. E. Johnson ◽  
G. C. Sieck
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Tracheal Smooth Muscle ◽  
Nitric Oxide Donor ◽  
Ip3 Receptors ◽  
Video Fluorescence Microscopy ◽  
Inositol 1,4,5 Trisphosphate

In the present study, effects of the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), on sarcoplasmic reticulum (SR) Ca2+ release were examined in freshly dissociated porcine tracheal smooth muscle (TSM) cells. Fura 2-loaded TSM cells were imaged using video fluorescence microscopy. SR Ca2+ release was induced by acetylcholine (ACh), which acts principally through inositol 1,4,5-trisphosphate (IP3) receptors, and by caffeine, which acts principally through ryanodine receptors (RyR). SNAP inhibited ACh-induced SR Ca2+ release at both 0 and 2.5 mM extracellular Ca2+. Degraded SNAP had no effect on ACh-induced SR Ca2+ release. SNAP also inhibited caffeine-induced SR Ca2+ release. ACh-induced Ca2+ influx was not affected by SNAP when SR reloading was blocked by thapsigargin. SNAP also did not affect SR Ca2+ reuptake. The membrane-permeant analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromo-cGMP, mimicked the effects of SNAP. These results suggest that, in porcine TSM cells, SNAP reduces the intracellular Ca2+ response to ACh and caffeine by inhibiting SR Ca2+ release through both IP3 and RyR, but not by inhibiting influx or repletion of the SR Ca2+ stores. These effects are likely mediated via cGMP-dependent mechanisms.

scholarly journals 80K-H Interacts with Inositol 1,4,5-Trisphosphate (IP3) Receptors and Regulates IP3-induced Calcium Release Activity

2008 ◽  
Vol 284 (1) ◽  
pp. 372-380 ◽  
Author(s):  
Katsuhiro Kawaai ◽  
Chihiro Hisatsune ◽  
Yukiko Kuroda ◽  
Akihiro Mizutani ◽  
Tomoko Tashiro ◽  
...  
Keyword(s):  
Calcium Release ◽  
Ip3 Receptors ◽  
Inositol 1,4,5 Trisphosphate

scholarly journals A Possible Anticancer Agent, Type III Interferon, Activates Cell Death Pathways and Produces Antitumor Effects

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Masatoshi Tagawa ◽  
Kiyoko Kawamura ◽  
Quanhai Li ◽  
Yuji Tada ◽  
Kenzo Hiroshima ◽  
...  
Keyword(s):  
Cell Death ◽  
Anticancer Agent ◽  
Receptor Expression ◽  
Type I ◽  
Functional Difference ◽  
Tumor Cell Death ◽  
Antitumor Effects ◽  
Type Iii ◽  
Wide Range ◽  
Type Iii Interferon

Recently identified interleukin-28 and -29 belong to a novel type III interferon (IFN) family, which could have distinct biological properties from type I and II IFNs. Type I IFNs, IFN-α/β, have been clinically applied for treating a certain kind of malignancies for over 30 years, but a wide range of the adverse effects hampered the further clinical applications. Type III IFNs, IFN-λs, have similar signaling pathways as IFN-α/βand inhibits proliferation of tumor cells through cell cycle arrest or apoptosis. Restricted patterns of type III IFN receptor expression in contrast to ubiquitously expressed IFN-α/βreceptors suggest that type III IFNs have limited cytotoxicity to normal cells and can be a possible anticancer agent. In this paper, we summarize the current knowledge on the IFN-λs-mediated tumor cell death and discuss the functional difference between type I and III IFNs.

scholarly journals A-current and type I/type II transition determine collective spiking from common input

2012 ◽  
Vol 108 (6) ◽  
pp. 1631-1645 ◽  
Author(s):  
Andrea K. Barreiro ◽  
Evan L. Thilo ◽  
Eric Shea-Brown
Keyword(s):  
Time Scales ◽  
Cell Populations ◽  
Type I ◽  
Time Lags ◽  
Type Ii ◽  
Neuron Models ◽  
Common Input ◽  
Time Constants ◽  
Long Time ◽  
Short Time

The mechanisms and impact of correlated, or synchronous, firing among pairs and groups of neurons are under intense investigation throughout the nervous system. A ubiquitous circuit feature that can give rise to such correlations consists of overlapping, or common, inputs to pairs and populations of cells, leading to common spike train responses. Here, we use computational tools to study how the transfer of common input currents into common spike outputs is modulated by the physiology of the recipient cells. We focus on a key conductance, gA, for the A-type potassium current, which drives neurons between “type II” excitability (low gA), and “type I” excitability (high gA). Regardless of gA, cells transform common input fluctuations into a tendency to spike nearly simultaneously. However, this process is more pronounced at low gA values. Thus, for a given level of common input, type II neurons produce spikes that are relatively more correlated over short time scales. Over long time scales, the trend reverses, with type II neurons producing relatively less correlated spike trains. This is because these cells' increased tendency for simultaneous spiking is balanced by an anticorrelation of spikes at larger time lags. These findings extend and interpret prior findings for phase oscillators to conductance-based neuron models that cover both oscillatory (superthreshold) and subthreshold firing regimes. We demonstrate a novel implication for neural signal processing: downstream cells with long time constants are selectively driven by type I cell populations upstream and those with short time constants by type II cell populations. Our results are established via high-throughput numerical simulations and explained via the cells' filtering properties and nonlinear dynamics.

scholarly journals The Common Inhalational Anesthetic Isoflurane Induces Apoptosis via  Activation of Inositol 1,4,5-Trisphosphate Receptors

2008 ◽  
Vol 108 (2) ◽  
pp. 251-260 ◽  
Author(s):  
Huafeng Wei ◽  
Ge Liang ◽  
Hui Yang ◽  
Qiujun Wang ◽  
Brian Hawkins ◽  
...  
Keyword(s):  
Calcium Release ◽  
B Lymphocyte ◽  
Receptor Activity ◽  
Wild Type ◽  
Ip3 Receptors ◽  
Ip3 Receptor ◽  
Knock Out ◽  
Inositol 1,4,5 Trisphosphate ◽  
Induced Apoptosis ◽  
Er Membrane

Background Isoflurane induces cell apoptosis by an unknown mechanism. The authors hypothesized that isoflurane activates inositol 1,4,5-trisphosphate (IP3) receptors on the endoplasmic reticulum (ER) membrane, causing excessive calcium release, triggering apoptosis. Methods The authors determined isoflurane-induced cytotoxicity by measuring caspase-3 activity, lactate dehydrogenase release, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) reduction, and imaging analysis of cell damage markers (annexin V and propidium iodide staining) in different cell types. The authors used the chicken B lymphocyte with a total knock-out of IP3 receptors, PC12 cells with elevated IP3 receptor activity (transfected with L286V presenilin 1), striatal cells with a knock-in of Q111 Huntingtin, and each cell line's corresponding wild-type controls. The authors also measured the isoflurane-evoked changes of calcium concentration in cytosol and/or mitochondria in these cells. Results Isoflurane induced apoptosis concentration- and time-dependently, and sequentially elevated cytosolic and then mitochondrial calcium in the chicken B-lymphocyte wild-type but not the IP3 receptor total knock-out cells. Thapsigargin, a calcium adenosine triphosphatase inhibitor on ER membranes, induced apoptosis and elevations of calcium in cytosol and mitochondria in both chicken B-lymphocyte wild-type and IP3 receptor total knock-out cells. Isoflurane induced significantly more neurotoxicity and greater calcium release from the ER in L286V PC12 and Q111 Huntingtin striatal cells than in their corresponding wild-type controls, both of which were significantly inhibited by the IP3 receptor antagonist xestospongin C. Conclusion These findings suggest that isoflurane activates the ER membrane IP3 receptor, producing excessive calcium release and triggering apoptosis. Neurons with enhanced IP3 receptor activity, as in certain cases of familial Alzheimer or Huntington disease, may be especially vulnerable to isoflurane cytotoxicity.

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