• The Korean Journal of Physiology and Pharmacology
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• v.18 no.4
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• pp.297-305
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• 2014

Flavonoids have an ability to suppress various ion channels. We determined whether one of flavonoids, cyanidin-3-glucoside, affects adenosine 5'-triphosphate (ATP)-induced calcium signaling using digital imaging methods for intracellular free $Ca^{2+}$ concentration ([$Ca^{2+}$]i), reactive oxygen species (ROS) and mitochondrial membrane potential in PC12 cells. Treatment with ATP ($100{\mu}M$) for 90 sec induced [$Ca^{2+}$]i increases in PC12 cells. Pretreatment with cyanidin-3-glucoside ($1{\mu}g/ml$ to $100{\mu}g/ml$) for 30 min inhibited the ATP-induced [$Ca^{2+}$]i increases in a concentration-dependent manner ($IC_{50}=15.3{\mu}g/ml$). Pretreatment with cyanidin-3-glucoside ($15{\mu}g/ml$) for 30 min significantly inhibited the ATP-induced [$Ca^{2+}$]i responses following removal of extracellular $Ca^{2+}$ or depletion of intracellular [$Ca^{2+}$]i stores. Cyanidin-3-glucoside also significantly inhibited the relatively specific P2X2 receptor agonist 2-MeSATP-induced [$Ca^{2+}$]i responses. Cyanidin-3-glucoside significantly inhibited the thapsigargin or ATP-induced store-operated calcium entry. Cyanidin-3-glucoside significantly inhibited the ATP-induced [$Ca^{2+}$]i responses in the presence of nimodipine and ${\omega}$-conotoxin. Cyanidin-3-glucoside also significantly inhibited KCl (50 mM)-induced [$Ca^{2+}$]i increases. Cyanidin-3-glucoside significantly inhibited ATP-induced mitochondrial depolarization. The intracellular $Ca^{2+}$ chelator BAPTA-AM or the mitochondrial $Ca^{2+}$ uniporter inhibitor RU360 blocked the ATP-induced mitochondrial depolarization in the presence of cyanidin-3-glucoside. Cyanidin-3-glucoside blocked ATP-induced formation of ROS. BAPTA-AM further decreased the formation of ROS in the presence of cyanidin-3-glucoside. All these results suggest that cyanidin-3-glucoside inhibits ATP-induced calcium signaling in PC12 cells by inhibiting multiple pathways which are the influx of extracellular $Ca^{2+}$ through the nimodipine and ${\omega}$-conotoxin-sensitive and -insensitive pathways and the release of $Ca^{2+}$ from intracellular stores. In addition, cyanidin-3-glucoside inhibits ATP-induced formation of ROS by inhibiting $Ca^{2+}$-induced mitochondrial depolarization.

• Journal of applied mathematics & informatics
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• v.31 no.5_6
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• pp.695-709
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• 2013

Calcium is well known role for signal transduction in a neuron cell. Various processes and parameters modulate the intracellular calcium signaling process. A number of experimental and theoretical attempts are reported in the literature for study of calcium signaling in neuron cells. But still the role of various processes, components and parameters involved in calcium signaling is still not well understood. In this paper an attempt has been made to develop two dimensional finite element model to study calcium diffusion in neuron cells. The JRyR, JSERCA and JLeak, the exogenous buffers like EGTA and BAPTA, and diffusion coefficients have been incorporated in the model. Appropriate boundary conditions have been framed. Triangular ring elements have been employed to discretized the region. The effect of these parameters on calcium diffusion has been studied with the help of numerical results.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.149-158
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• 2003

Objective : The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide, sodium nitroprusside and hydrogen peroxide induced expression phospholipase $A_2$ and calcium concentration in RAW 264.7 cells, a murine macrophage cell line. Method : The expression of phospholipase $A_2$ was determined by western blotting with corresponding antibodies, and the generation of intracellular calcium concentration was investigated by delta scan system in RAW 264.7 cells. Results : 1. Compared with control, expressions of lipopolysaccharide-induced phospholipase $A_2$ were decreased significantly by $1\;{\mu}g/{\mu}l$ of bee venom and decreased by 0.5, $5\;{\mu}g/{\mu}l$ of bee venom. 2. Compared with control, expressions of sodium nitroprusside-induced phospholipase $A_2$ were decreased significantly by $5\;{\mu}g/{\mu}l$ of bee venom but increased by 0.5, $5\;{\mu}g/{\mu}l$ of bee venom. 3. Compared with control, expressions of hydrogen peroxide-induced phospholipase $A_2$ were decreased significaltly by $1{\mu}g/{\mu}l$ of bee venom and decreased by $0.5\;{\mu}g/{\mu}l$ of bee venom but increased by $5\;{\mu}g/{\mu}l$ of bee venom. 4. Compared with control, lipopolysaccharide, sodium nitroprusside and hydrogen peroxide- induced intracellular calcium concentrations were decreased by 0.5, 1, $5\;{\mu}g/{\mu}l$ of bee venom and by indomethacin

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.277-286
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• 2020

Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin-L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM N-lobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu-593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.

• Journal of Acupuncture Research
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• v.21 no.5
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• pp.179-190
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• 2004

Objectives : The purpose of this study was to investigate the effect of Bee Venom and Melittin acupuncture solution on the lipopolysaccharide and sodium nitroprusside- induced expression of cytosolic phospholipase $A_2$, tumor necrosis factor-${\alpha}$ and calcium concentration in RAW 264.7 cells, a murine macrophage cell line. Methods : The expression of cytosolic phospholipase $A_2$ and tumor necrosis factor-${\alpha}$ was determined by western blotting with corresponding antibodies, and the generation of intracellular calcium concentration was investigated by delta scan system in RAW 264.7 cells. Results : 1. Compared with control, expressions of lipopolysaccharide-induced cytosolic phospholipase $A_2$ were decreased significantly by $5{\mu}g/mL$ of bee venom and 5, $10{\mu}g/mL$ of melittin acupuncture solution and decreased by 0.5, $1{\mu}g/mL$ of bee venom. 2. Compared with control, expressions of sodium nitroprusside-induced phospholipase $A_2$ were decreased significantly by 0.5, 1, $5{\mu}g/mL$ of bee venom and by 5, $10{\mu}g/mL$ of melittin acupuncture solution. 3. Compared with control, expressions of lipopolysaccharide-induced tumor necrosis factor-${\alpha}$ were decreased significantly by $10{\mu}g/mL$ of melittin acupuncture solution and were not changed significantly by 0.5, 1, $5{\mu}g/mL$ of bee venom and $5{\mu}g/mL$ of melittin acupuncture solution. 4. Compared with control, expressions of sodium nitroprusside-induced tumor necrosis factor-${\alpha}$ were decreased significantly by 1, $5{\mu}g/mL$ of bee venom and 5, $10{\mu}g/mL$ of melittin acupuncture solution and decreased by $0.5{\mu}g/mL$ of bee venom 5. Compared with control, lipopolysaccharide-induced intracellular calcium concentrations were decreased by 0.5, 1, $5{\mu}g/mL$ of bee venom and $10{\mu}g/mL$ of melittin acupuncture solution and increased by $5{\mu}g/mL$ of melittin acupuncture solution. 6. Compared with control, sodium nitroprusside-induced intracellular calcium concentrations were decreased by 0.5, 1, $5{\mu}g/mL$ of bee venom and 5, $10{\mu}g/mL$ of melittin acupuncture solution.

• Journal of Chest Surgery
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• v.23 no.1
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• pp.1-8
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• 1990

This experiment was carried out under the postulation that activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine[TFP], a calmodulin antagonist, was added to the potassium cardioplegic solution and used just before ischemia, and its protective effect from ischemic injury was investigated, using Langendorff rat heart model. TFP group had better post-ischemic functional recovery and lower post-ischemic contracture after 30 minutes of normothermic ischemia. Creatine kinase leakage was also decreased in TFP group but there was no statistical difference between control group and TFP group. We concluded that TFP has some protective effect from myocardial ischemic injury and its effect might be due to prevention of activation of intracellular calcium-calmodulin complex.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.1-8
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• 2013

Understanding the cellular and molecular mechanisms involved in the development and progression of pulmonary hypertension (PH) remains imperative if we are to successfully improve the quality of life and life span of patients with the disease. A whole plethora of mechanisms are associated with the development and progression of PH. Such complexity makes it difficult to isolate one particular pathway to target clinically. Changes in intracellular free calcium concentration, the most common intracellular second messenger, can have significant impact in defining the pathogenic mechanisms leading to its development and persistence. Signaling pathways leading to the elevation of $[Ca^{2+}]_{cyt}$ contribute to pulmonary vasoconstriction, excessive proliferation of smooth muscle cells and ultimately pulmonary vascular remodeling. This current review serves to summarize the some of the most recent advances in the regulation of calcium during pulmonary hypertension.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.85-90
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• 2017

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

• YAKHAK HOEJI
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• v.39 no.6
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• pp.616-621
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• 1995

The effect of WK101 on compound 48/80-induced anaphylaxis was studied in rat. WK101 was found to exhibit a inhibitory activity on the compound 48/80-induced anaphylaxis. WK101 also inhibited the serum histamine release induced in anaphylaxis by compound 48/80. The effect of WK101 on the histamine release from rat peritoneal mast cells was studied. WK101 ($10^{3}-1mg/ml$) inhibited the histamine release induced by compound 48/80($5{\;}\mu\textrm{g}/ml$) in rat peritoneal mast cells. To clarify the mechanism of these inhibitons, we investigated the effects of WK101 on cAMP and intracellular calcium content of rat peritoneal mast cell. The content of cAMP in mast cells, when WK101 was added, was increased transiently, and was significantly increased more 53 fold at 10 sec than that of basal cells. Moreover, WK101 inhibited intracellular calcium release induced by compoound 48/80. This results suggest that WK101 may be useful for the prevention and treatment of allergy-related disease.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.132-136
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• 1996

Exogenously applied oxygen free radical generating agent, pyrogallol, highly elevated extracellular glutamate accumulation and augmented N-methyl-D-aspartate (NMDA)-induced glutamate accumulation in cerebellar granule neuronal cells, but did not in astrocytes. Superoxide dismutase remarkably decreased the pyrogallol-induced glutamate accumulation, but either NMDA or kainate antagonists did not. In addition, pyrogallol did not affect the NMDAinduced intracellular calcium elevation. Pyrogallol partially blocked glutamate uptake into astrocytes. These results suggest that oxygen free radicals elevate extracellular glutamate accumulation by stimulating the release of glutamate as well as blocking the glutamate uptake.