• International Journal of Oral Biology
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• 제45권2호
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• pp.58-63
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• 2020

The salivary glands secrete saliva, which plays a role in the maintenance of a healthy oral environment. Under physiological conditions, saliva secretion within the acinar cells of the gland is regulated by stimulation of specific calcium (Ca²⁺) signaling mechanisms such as increases in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) via storeoperated Ca²⁺ entry, which involves components such as Orai1, transient receptor potential (TRP) canonical 1, stromal interaction molecules, and inositol 1,4,5-triphosphate (IP₃) receptors (IP₃Rs). Homer proteins are scaffold proteins that bind to G protein-coupled receptors, IP₃Rs, ryanodine receptors, and TRP channels. However, their exact role in Ca²⁺ signaling in the salivary glands remains unknown. In the present study, we investigated the role of Homer2 in Ca²⁺ signaling and saliva secretion in parotid gland acinar cells under physiological conditions. Deletion of Homer2 (Homer2^-/-) markedly decreased the amplitude of [Ca²⁺]_i oscillations via the stimulation of carbachol, which is physiologically concentrated in parotid acinar cells, whereas the frequency of [Ca²⁺]_i oscillations showed no difference between wild-type and Homer2^-/- mice. Homer2^-/- mice also showed a significant decrease in amylase release by carbachol in the parotid gland in a dose-dependent manner. These results suggest that Homer2 plays a critical role in maintaining [Ca²⁺]_i concentration and secretion of saliva in mouse parotid gland acinar cells.

• International Journal of Oral Biology
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• 제46권4호
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

• BMB Reports
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• 제55권11호
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• pp.528-534
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• 2022

Mitochondria are cellular organelles that perform various functions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca²⁺ ions for their activity, mitochondria have ion channels to selectively uptake Ca²⁺ ions from the cytoplasm. The ion channel known to play the most important role in the Ca²⁺ uptake in mitochondria is the mitochondrial calcium uniporter (MCU) holo-complex located in the inner mitochondrial membrane (IMM). This ion channel complex exists in the form of a complex consisting of the pore-forming protein through which the Ca²⁺ ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca²⁺ uptake by the MCU holo-complex. Studies of this MCU holo-complex have long been conducted, but we didn't know in detail how mitochondria uptake Ca²⁺ ions through this ion channel complex or how the activity of this ion channel complex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca²⁺ uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of action of the MCU holo-complex at the molecular level based on the Cryo-EM structure of the MCU holo-complex to help understand how mitochondria uptake the necessary Ca²⁺ ions through the MCU holo-complex and how these Ca²⁺ uptake mechanisms are regulated.

• Journal of the Korean Chemical Society
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• 제53권3호
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• pp.272-278
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• 2009

The optimized structures and vibrational frequencies for $Ca^+-(CO)_n$ and $Ca^+-(CO_2)_n$ (n=1,2) complexes were calculated with MP2 and B3LYP methods employing 6-311++G(2d,p) basis sets. Also the binding energies were investigated for all complexes to compare the stabilities. For $Ca^+-(CO)_n$ C-bonded complexes are more stable than O-bonded complexes. Two stable conformations, linear and $C_{2v}$ form, are possible for $Ca^+-(CO)_2$ complexes and the $C_{2v}$ form is more stable than the linear form. $Ca^+-(CO_2)_2$ also has two possible conformations and linear form has slightly lower energy than $C_{2v}$ form.

• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.531-540
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• 2022

Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca²⁺ concentration ([Ca²⁺]_i) spikes and neuronal cell death induced by 0.1 mM Mg²⁺ and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using imaging methods for Ca²⁺ and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg²⁺ concentration ([Mg²⁺]_o) to 0.1 mM induced repetitive [Ca²⁺]_i spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca²⁺]_i spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca²⁺]_i spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The IP₃ receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca²⁺]_i spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca²⁺ from IP₃ and ryanodine-sensitive intracellular stores and activating TRPC channels.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.287-298
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• 2020

Ca²⁺ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca²⁺ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca²⁺ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K⁺ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca²⁺ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca²⁺-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca²⁺-sensitive K⁺ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca²⁺ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca²⁺ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

• Molecules and Cells
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• 제19권2호
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• pp.268-278
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• 2005

We investigated the effect of cytosolic and extracellular $Ca^{2+}$ on $Ca^{2+}$ signals in pancreatic acinar cells by measuring $Ca^{2+}$ concentration in the cytosol($[Ca^{2+}]_c$) and in the lumen of the ER($[Ca^{2+}]_{Lu}$). To control buffers and dye in the cytosol, a patch-clamp microelectrode was employed. Acetylcholine released $Ca^{2+}$ mainly from the basolateral ER-rich part of the cell. The rate of $Ca^{2+}$ release from the ER was highly sensitive to the buffering of $[Ca^{2+}]_c$ whereas ER $Ca^{2+}$ refilling was enhanced by supplying free $Ca^{2+}$ to the cytosol with $[Ca^{2+}]_c$ clamped at resting levels with a patch pipette containing 10 mM BAPTA and 2 mM $Ca^{2+}$. Elevation of extracellular $Ca^{2+}$ to 10 mM from 1 mM raised resting $[Ca^{2+}]_c$ slightly and often generated $[Ca^{2+}]_c$ oscillations in single or clustered cells. Although pancreatic acinar cells are reported to have extracellular $Ca^{2+}$-sensing receptors linked to phospholipase C that mobilize $Ca^{2+}$ from the ER, exposure of cells to 10 mM $Ca^{2+}$ did not decrease $[Ca^{2+}]_{Lu}$ but rather raised it. From these findings we conclude that 1) ER $Ca^{2+}$ release is strictly regulated by feedback inhibition of $[Ca^{2+}]_c$, 2) ER $Ca^{2+}$ refilling is determined by the rate of $Ca^{2+}$ influx and occurs mainly in the tiny subplasmalemmal spaces, 3) extracellular $Ca^{2+}$-induced $[Ca^{2+}]_c$ oscillations appear to be triggered not by activation of extracellular $Ca^{2+}$-sensing receptors but by the ER sensitised by elevated $[Ca^{2+}]_c$ and $[Ca^{2+}]_{Lu}$.

• Journal of People, Plants, and Environment
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• 제23권4호
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• pp.445-453
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• 2020

Background and objective: Calcium chloride (CaCl₂) and sodium chloride (NaCl) are commonly used as a deicing agent in South Korea and penetrate the soil on the roadside, causing damage to plants. This study was conducted to investigate the salinity reduction effect of Pennisetum alopecuroides and the chemical characteristics of soil leachate. Methods: The plants were treated with five different concentrations of CaCl₂ (0, 1, 2, 5, and 10g·L^-1) and were grouped into the Cont., C1, C2, C5, and C10 groups. CaCl₂ of 200 m·L^-1 was sprayed to each plant once every two weeks. The growth of P. alopecuroides (plant height, leaf length, leaf width and the number of leaves) was measured. The level of EC and pH, and exchangeable cations (K⁺, Ca²⁺, Na⁺, and Mg²⁺) in the leachate of soil was monitored. Results: The pH of soil leachate decreased as the CaCl₂ concentration increased, and the EC increased significantly. The content of K⁺ did not change significantly until the concentration of CaCl₂ reached 5 g·L^-1, but the content of Ca²⁺, Na⁺, and Mg²⁺ significantly increased. The plant height, leaf length, and leaf width of P. alopecuroides showed the highest value in CaCl₂ 1 g·L^-1 followed by CaCl₂ 2 g·L^-1 and the control group. Root fresh weight was the highest in CaCl₂ 2 g·L^-1. On the other hand, there was no change in the shoot fresh weight, dry weight and root dry weight, and P. alopecuroides growth inhibition at the concentration of 5 g·L^-1 or higher in the plant height and leaf length. Conclusion: P. alopecuroides is relatively highly salt-tolerant and can improve the salt damaged soil by lowering the content of the salt-based exchangeable K⁺ ions.

• Journal of Korean Society of Water and Wastewater
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• 제35권2호
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• pp.113-120
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• 2021

High voltage impulse (HVI) has been gained attention as an alternative technique that could control the CaCO₃ scale problems encountered in water main, pipe, cooling tower and heat exchanger vessels. The aim of this study was to investigate the effect of electric field (E) and contact time (t) of HVI on reduction of Ca²⁺ concentration at two different temperatures of 25℃ and 60℃. A kinetic model on the effect of E and t was investigated too. As the E and t increased, the Ca²⁺ concentration decreased more than that of the control (= no HVI). The Ca²⁺ concentration decreased up to 81% at 15 kV/cm at 60℃, which was nearly 2 times greater than the control. With these experimental data-set of reduction of Ca²⁺ concentration under different E and t, the kinetic model was developed. The relationship between E and t required to reduce the concentration of Ca²⁺ by 30% was modeled at each temperature. The empirical model equations were; E^0.83· t = 60.3 at 25℃ and E^0.08· t = 1.1 at 60℃. These equations state the products of Eⁿ and t is always constant, which means that the required contact time can be reduced in accordance with the increment of E and vice versa.

• Korean Journal of Crystallography
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• 제13권1호
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• pp.25-30
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• 2002

The M/sub 1-x/Na/sub 2x/Al₂(BO₃)₂O (M = Ca and Sr) solid solution systems have been shown interstitial solid solutions and continuous substitutional solid solutions. The symmetry around the Eu site of yEu/sup 3+/ : M/sub 1-x/Na/sub 2x/Al/sub 2-y/Mg/sub /(BO₃)₂O (M = Ca and Sr) changes the intensities and the chromaticities of transitions. The Eu/sup 3+/ion can be very bright and efficient and have the desired emission wave-length depending on the site symmetry of the Eu/sup 3+/ion site. As the amount of Na in the Eu/sup 3+/ion doped Ca/sub 1-x/Na/sub 2x/Al₂(BO₃)₂O system increases, the Eu site symmetry is going to be a noncentrosymmetric site. With increasing x, the decreased intensity in the /sup 5/D/sub 0/→/sup 7/F₁(590 nm) transition relates to the low symmetry of the Eus/up 3+/-doped Ca/sub 1-x/Na/sub 2x/Al₂(BO₃)₂O system, because of the Ca-centered octahedron in the CaAl₂(BO₃)₂O compound. The SrAl₂(BO₃)₂O compound also provides an improved chromaticity due to the lower site symmetry of Eu/sup 3+/ion.