scholarly journals Store-operated calcium entry in physiology and pathology of mammalian cells.

2005 ◽  
Vol 52 (2) ◽  
pp. 397-409 ◽  
Author(s):  
Berenika Targos ◽  
Jolanta Barańska ◽  
Paweł Pomorski
Keyword(s):  
Cell Cycle ◽  
Calcium Level ◽  
Mammalian Cells ◽  
Long Term Potentiation ◽  
Calcium Entry ◽  
Neuroendocrine Cells ◽  
Calcium Stores ◽  
Excitable Cells ◽  
Store Operated Calcium Entry ◽  
Er Calcium

One of the numerous calcium-involving processes in mammalian cells is store-operated calcium entry (SOCE) -- the process in which depletion of calcium stores in the endoplasmic reticulum (ER) induces calcium influx from the extracellular space. Previously supposed to function only in non-excitable cells, SOCE is now known to play a role also in such excitable cells as neurons, muscles and neuroendocrine cells and is found in many different cell types. SOCE participates not only in processes dependent on ER calcium level but also specifically regulates some important processes such as cAMP production, T lymphocyte activation or induction of long-term potentiation. Impairment of SOCE can be an element of numerous disorders such as acute pancreatitis, primary immunodeficiency and, since it can take part in apoptosis or cell cycle regulation, SOCE may also be partially responsible for such serious disorders as Alzheimer disease and many types of cancer. Even disturbances in the 'servant' role of maintaining ER calcium level may cause serious effects because they can lead to ER homeostasis disturbance, influencing gene expression, protein synthesis and processing, and the cell cycle.

scholarly journals Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range

2020 ◽  
Vol 21 (24) ◽  
pp. 9777
Author(s):  
Camille Le Guilcher ◽  
Tomas Luyten ◽  
Jan B. Parys ◽  
Mathieu Pucheault ◽  
Olivier Dellis
Keyword(s):  
Cell Activation ◽  
Interleukin 2 ◽  
Calcium Entry ◽  
Ip3 Receptors ◽  
Excitable Cells ◽  
Cellular Targets ◽  
Entry Inhibitors ◽  
The Past ◽  
Store Operated Calcium Entry

The store-operated calcium entry, better known as SOCE, forms the main Ca2+ influx pathway in non-excitable cells, especially in leukocytes, where it is required for cell activation and the immune response. During the past decades, several inhibitors were developed, but they lack specificity or efficacy. From the non-specific SOCE inhibitor 2-aminoethyl diphenylborinate (2-APB), we synthetized 16 new analogues by replacing/modifying the phenyl groups. Among them, our compound P11 showed the best inhibitory capacity with a Ki ≈ 75 nM. Furthermore, below 1 µM, P11 was devoid of any inhibitory activity on the two other main cellular targets of 2-APB, the IP3 receptors, and the SERCA pumps. Interestingly, Jurkat T cells secrete interleukin-2 under phytohemagglutinin stimulation but undergo cell death and stop IL-2 synthesis when stimulated in the presence of increasing P11 concentrations. Thus, P11 could represent the first member of a new and potent family of immunosuppressors.

Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons

Cell Calcium ◽  
2015 ◽  
Vol 58 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Samira Samtleben ◽  
Britta Wachter ◽  
Robert Blum
Keyword(s):  
Hippocampal Neurons ◽  
Calcium Entry ◽  
Store Operated Calcium Entry ◽  
Calcium Loss ◽  
Er Calcium

scholarly journals Calcium Sensors STIM1 and STIM2 Regulate Different Calcium Functions in Cultured Hippocampal Neurons

2021 ◽  
Vol 12 ◽  
Author(s):  
Liliya Kushnireva ◽  
Eduard Korkotian ◽  
Menahem Segal
Keyword(s):  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Calcium Entry ◽  
Calcium Stores ◽  
Plastic Properties ◽  
Calcium Sensors ◽  
Central Neurons ◽  
Transient Rise ◽  
Store Operated Calcium Entry ◽  
Adult Neuron

There are growing indications for the involvement of calcium stores in the plastic properties of neurons and particularly in dendritic spines of central neurons. The store-operated calcium entry (SOCE) channels are assumed to be activated by the calcium sensor stromal interaction molecule (STIM)which leads to activation of its associated Orai channel. There are two STIM species, and the differential role of the two in SOCE is not entirely clear. In the present study, we were able to distinguish between transfected STIM1, which is more mobile primarily in young neurons, and STIM2 which is less mobile and more prominent in older neurons in culture. STIM1 mobility is associated with spontaneous calcium sparks, local transient rise in cytosolic [Ca2+]i, and in the formation and elongation of dendritic filopodia/spines. In contrast, STIM2 is associated with older neurons, where it is mobile and moves into dendritic spines primarily when cytosolic [Ca2+]i levels are reduced, apparently to activate resident Orai channels. These results highlight a role for STIM1 in the regulation of [Ca2+]i fluctuations associated with the formation of dendritic spines or filopodia in the developing neuron, whereas STIM2 is associated with the maintenance of calcium entry into stores in the adult neuron.

scholarly journals Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

2010 ◽  
Vol 298 (5) ◽  
pp. C1127-C1139 ◽  
Author(s):  
Kiyoshi Itagaki ◽  
Michael Menconi ◽  
Bozena Antoniu ◽  
Qin Zhang ◽  
Patricia Gonnella ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Protein Degradation ◽  
Intracellular Calcium ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Calcium Entry ◽  
Calcium Stores ◽  
Fluorescence Measurements ◽  
Store Operated Calcium Entry

Muscle wasting in various catabolic conditions is at least in part regulated by glucocorticoids. Increased calcium levels have been reported in atrophying muscle. Mechanisms regulating calcium homeostasis in muscle wasting, in particular the role of glucocorticoids, are poorly understood. Here we tested the hypothesis that glucocorticoids increase intracellular calcium concentrations in skeletal muscle and stimulate store-operated calcium entry (SOCE) and that these effects of glucocorticoids may at least in part be responsible for glucocorticoid-induced protein degradation. Treatment of cultured myotubes with dexamethasone, a frequently used in vitro model of muscle wasting, resulted in increased intracellular calcium concentrations determined by fura-2 AM fluorescence measurements. When SOCE was measured by using calcium “add-back” to muscle cells after depletion of intracellular calcium stores, results showed that SOCE was increased 15–25% by dexamethasone and that this response to dexamethasone was inhibited by the store-operated calcium channel blocker BTP2. Dexamethasone treatment stimulated the activity of calcium-independent phospholipase A2(iPLA2), and dexamethasone-induced increase in SOCE was reduced by the iPLA2inhibitor bromoenol lactone (BEL). In additional experiments, treatment of myotubes with the store-operated calcium channel inhibitor gadolinium ion or BEL reduced dexamethasone-induced increase in protein degradation. Taken together, the results suggest that glucocorticoids increase calcium concentrations in myocytes and stimulate iPLA2-dependent SOCE and that glucocorticoid-induced muscle protein degradation may at least in part be regulated by increased iPLA2activity, SOCE, and cellular calcium levels.

scholarly journals Relocalization of STIM1 in mouse oocytes at fertilization: early involvement of store-operated calcium entry

Reproduction ◽  
2009 ◽  
Vol 138 (2) ◽  
pp. 211-221 ◽  
Author(s):  
Carolina Gómez-Fernández ◽  
Eulalia Pozo-Guisado ◽  
Miguel Gañán-Parra ◽  
Mario J Perianes ◽  
Ignacio S Álvarez ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Calcium Entry ◽  
Calcium Stores ◽  
Calcium Waves ◽  
Resting Cells ◽  
Metaphase Arrest ◽  
Mouse Oocytes ◽  
Store Depletion ◽  
Store Operated Calcium Entry ◽  
Mature Mouse

Calcium waves represent one of the most important intracellular signaling events in oocytes at fertilization required for the exit from metaphase arrest and the resumption of the cell cycle. The molecular mechanism ruling this signaling has been described in terms of the contribution of intracellular calcium stores to calcium spikes. In this work, we considered the possible contribution of store-operated calcium entry (SOCE) to this signaling, by studying the localization of the protein STIM1 in oocytes. STIM1 has been suggested to play a key role in the recruitment and activation of plasma membrane calcium channels, and we show here that mature mouse oocytes express this protein distributed in discrete clusters throughout their periphery in resting cells, colocalizing with the endoplasmic reticulum marker calreticulin. However, immunolocalization of the endogenous STIM1 showed considerable redistribution over larger areas or patches covering the entire periphery of the oocyte during Ca2+ store depletion induced with thapsigargin or ionomycin. Furthermore, pharmacological activation of endogenous phospholipase C induced a similar pattern of redistribution of STIM1 in the oocyte. Finally, fertilization of mouse oocytes revealed a significant and rapid relocalization of STIM1, similar to that found after pharmacological Ca2+ store depletion. This particular relocalization supports a role for STIM1 and SOCE in the calcium signaling during early stages of fertilization.

scholarly journals STIM-Orai1 signaling regulates fluidity of cytoplasm during membrane blebbing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kana Aoki ◽  
Shota Harada ◽  
Keita Kawaji ◽  
Kenji Matsuzawa ◽  
Seiichi Uchida ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Calcium Concentration ◽  
Calcium Entry ◽  
Cytoplasmic Calcium ◽  
Sharp Rise ◽  
Membrane Blebbing ◽  
Actin Cortex ◽  
Membrane Blebs ◽  
Store Operated Calcium Entry

AbstractThe cytoplasm in mammalian cells is considered homogeneous. In this study, we report that the cytoplasmic fluidity is regulated in the blebbing cells; the cytoplasm of rapidly expanding membrane blebs is more disordered than the cytoplasm of retracting blebs. The increase of cytoplasmic fluidity in the expanding bleb is caused by a sharp rise in the calcium concentration. The STIM-Orai1 pathway regulates this rapid and restricted increase of calcium in the expanding blebs. Conversely, activated ERM protein binds to Orai1 to inhibit the store-operated calcium entry in retracting blebs, which results in decreased in cytoplasmic calcium, rapid reassembly of the actin cortex.

scholarly journals Orai1 and Stim1 Mediate the Majority of Store-Operated Calcium Entry in Multiple Myeloma and Have Strong Implications for Adverse Prognosis

2018 ◽  
Vol 48 (6) ◽  
pp. 2273-2285 ◽  
Author(s):  
Wei Wang ◽  
Yuyue Ren ◽  
Lianjie Wang ◽  
Weiwei Zhao ◽  
Xiushuai Dong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Viability ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Annexin V ◽  
Hematologic Malignancies ◽  
Calcium Entry ◽  
Cycle Arrest ◽  
Store Operated Calcium Entry

Background/Aims: Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite the development and application of novel agents, MM still undergoes an aggressive and incurable course in the vast majority of patients. Ca2+ is one of the critical regulators of cell migration. Ca2+ influx is essential for the migration of various types of cells including tumor cells. However, the role of store-operated calcium entry (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been reported in MM cell survival. Methods: We evaluated the expression of Stim1 and Orai1 (two key regulators of SOC) in MM tissues and cell lines by immunohistochemical assay, quantitative real-time PCR assay and western blot. MM cell lines were pretreated with pharmacological blockers and siRNAs, and then MM cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the expression of Stim1 (or Orai1) level and outcome in MM were assessed by using Progress Free Survival (PFS). Results: Stim1 and Orai1 were both abundantly expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated with the clinical outcome of MM. Conclusion: The Stim1/Orai1-mediated signaling participates in the pathogenesis of MM, which represents an attractive target for future therapeutic intervention.

Impairment of Store-operated Calcium Entry: Implications in Alzheimer’s Neurodegeneration

2021 ◽  
Vol 17 (12) ◽  
pp. 1088-1094
Author(s):  
Jing Zhou ◽  
Shengzhou Wu
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Alternative Hypothesis ◽  
Cholinergic Neurons ◽  
Proteasome Inhibition ◽  
Calcium Entry ◽  
Calcium Sensors ◽  
Store Operated Calcium Entry ◽  
Er Calcium

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder. Dysfunction of central cholinergic neurons, amyloid aggregation and deposition,oxidative stress,and biometal dyshomeostasis has been regarded as the major pathogenic mediators in this devastating disease. However, strategies derived from these hypotheses fail to slow down or stop the progression of AD, warranting a combination of therapies to target multiple etiological factors or examining alternative hypothesis. Store-operated calcium entry (SOCE) is the process by which depletion of calcium in the endoplasmic reticulum (ER) lumen causes an influx of calcium across plasmalemma. Accumulating evidence indicates that neuronal SOCE (nSOCE) is inhibited in family AD (FAD) and the inhibition of which causes instability of dendritic spines and enhances amyloidogenesis. Mutant Presenilin fails to function as an ER calcium leak channel and promotes degradation of stromal interaction molecules (STIM), ER calcium sensors; these effects may account for the repression of nSOCE in FAD. We have demonstrated that activation of autophagy degrades STIM proteins, resulting in a trimming effect on a dendritic arbor, under proteasome inhibition and endoplasmic reticulum stress, which are intimately connected with AD. Thus, we hypothesize that autophagy represses SOCE by degrading STIM proteins, leading to synapse loss in AD. This review article will highlight the roles of SOCE in AD neurodegeneration, the degradative mechanisms of STIM protein, and the therapeutic potential and associated challenge.

scholarly journals Effect of Azumolene on RyR1-Dependent Store Operated Calcium Entry in RyR1-Expressing, Non Excitable Cells

2010 ◽  
Vol 98 (3) ◽  
pp. 546a
Author(s):  
Balazs Lukacs ◽  
Daniela Requena ◽  
Sutanu Samanta ◽  
Jerome Parness
Keyword(s):  
Calcium Entry ◽  
Excitable Cells ◽  
Store Operated Calcium Entry
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