• Title/Summary/Keyword: activated calcium

Search Result 358, Processing Time 0.036 seconds

ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells

  • Arduino, Daniela M.;Esteves, A. Raquel;Domingues, A. Filipa;Pereira, Claudia M.F.;Cardoso, Sandra M.;Oliveira, Catarina R.
    • BMB Reports
    • /
    • v.42 no.11
    • /
    • pp.719-724
    • /
    • 2009
  • Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

The Characterization of the Increase of Membrane Conductance after Depolarization in Single Rat Adrenal Chromaffin Cells

  • Lim, Won-Il;Kim, Sang-Jeong;Kim, Jun
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.2 no.1
    • /
    • pp.95-100
    • /
    • 1998
  • The conductance change evoked by step depolarization was studied in primarily cultured rat adrenal chromaffin cells using patch-clamp and capacitance measurement techniques. When we applied a depolarizing pulse to a chromaffin cell, the inward calcium current was followed by an outward current and depolarization-induced exocytosis was accompanied by an increase in conductance trace. The slow inward tail current which has the same time course as the conductance change was observed in current recording. The activation of slow tail current was calcium-dependent. Reversal potentials agreed with Nernst equation assuming relative permeability of $Cs^+\;to\;K^+$ is 0.095. The outward current and tail current were blocked by apamin (200 nM) and d-tubocurarine (2 mM). The conductance change was blocked by apamin and did not affect membrane capacitance recording. We confirmed that conductance change after depolarization comes from the activation of the SK channel and can be blocked by application of the SK channel blockers. Consequently, it is necessary to consider blocking of the SK channel during membrane capacitance recording.

  • PDF

Tusc2/Fus1 regulates osteoclast differentiation through NF-κB and NFATc1

  • Kim, Inyoung;Kim, Jung Ha;Kim, Kabsun;Seong, Semun;Kim, Nacksung
    • BMB Reports
    • /
    • v.50 no.9
    • /
    • pp.454-459
    • /
    • 2017
  • Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and $Ca^{2+}$-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B ($NF-{\kappa}B$) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. In contrast, small interfering RNA-mediated knockdown of Tusc2 strongly inhibited osteoclast differentiation. In addition, Tusc2 induced the activation of RANKL-mediated $NF-{\kappa}B$ and calcium/calmodulin-dependent kinase IV (CaMKIV)/cAMP-response element (CRE)-binding protein CREB signaling cascades. Taken together, these results suggest that Tusc2 acts as a positive regulator of RANKL-mediated osteoclast differentiation.

Effects of Activated Calcium on the Quality and Shelf-life of Wet Noodle (산화칼슘 첨가가 생면의 저장성에 미치는 영향)

  • Sung, Jee-Hye;Kim, Ro-Sa;Moon, Ji-Hye;Park, Ho-Young;Choi, Hee-Don;Kim, Yoon-Sook
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.39 no.9
    • /
    • pp.1373-1378
    • /
    • 2010
  • This study investigated the utilization of activated calcium (AC) as preservatives for wet noodle manufacturing. The quality characteristics and shelf-life of wet noodle made with sterilized distilled water, 5% alcohol, 0.1% AC plus 5% alcohol, 0.2% AC plus 5% alcohol, and 0.2% AC were evaluated. The total microbial count and pH value of wet noodle were determined during storage at $10^{\circ}C$. During storage at $10^{\circ}C$ for 42 days, pH of wet noodles was slightly decreased with increased storage periods. The pH values of wet noodles made with AC were higher than the others. Instrument textural characteristics (hardness, adhesiveness, springiness, cohesiveness, gumminess, and chewingness) were measured and were not significantly changed during storage period. The total microbial counts in wet noodles increased with extended storage duration. With AC, microbial growth rate were decreased compared to the control for whole storage period. In sensory evaluation, a little difference was shown between control and AC or alcohol containing wet noodles and no significant differences during the storage period. It was concluded that shelf-life of wet noodles was extended two-fold or more by adding AC for storage at $10^{\circ}C$.

Afatinib Mediates Autophagic Degradation of ORAI1, STIM1, and SERCA2, Which Inhibits Proliferation of Non-Small Cell Lung Cancer Cells

  • Kim, Mi Seong;Kim, So Hui;Yang, Sei-Hoon;Kim, Min Seuk
    • Tuberculosis and Respiratory Diseases
    • /
    • v.85 no.2
    • /
    • pp.147-154
    • /
    • 2022
  • Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca2+ entry (SOCE)-related proteins and intracellular Ca2+ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca2+ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca2+. Moreover, extracellular Ca2+ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca2+. Conclusion: Extracellular Ca2+ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca2+ is essential for determining anti-cancer drug efficacy.

Hyposmotic Cell Stretch Increases L-type Calcium Current in Smooth Muscle Cells of the Human Stomach

  • Kang, Tong-Mook;Kim, Chun-Hee;Kim, Min-Jung;Park, Myoung-Kyu;Uhm, Dae-Yong;Rhee, Jong-Chul;Rhee, Poong-Lyul
    • Proceedings of the Korean Biophysical Society Conference
    • /
    • 1998.06a
    • /
    • pp.39-39
    • /
    • 1998
  • Stretch-activated ion channel that is open by mechanical stress applied on the cell membrane is one of the classes of ion channels. Other than stretch-activated channel itself, it has been also reported that a variety of ion channels could be modulated by a mechanical cell stretch.(omitted)

  • PDF

Anti-allergic Effects of Artemisia iwayomogi on Animal Models of Allergic Reactions

  • Shin, Tae-Yong;Shin, Hye-Young;Kim, Hyung-Min
    • Natural Product Sciences
    • /
    • v.10 no.1
    • /
    • pp.24-28
    • /
    • 2004
  • The effects of aqueous extract of Artemisia iwayomogi (Compositae) (AIAE) on the mast cell-dependent allergic and inflammatory reactions were investigated. AIAE (0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in mice. AIAE (0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. AIAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80. Moreover, AIAE inhibited the secretion of interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.

Molecular Cloning and Characterization of Neuronal $\beta$-subunit of Large-Conductance$Ca^{2+}$-activated $K^+$ Channels from Rat Brain

  • Heo, Moon-Sun;Ha, Tal-Soo;Park, Chul-Seung
    • Proceedings of the Korean Biophysical Society Conference
    • /
    • 2001.06a
    • /
    • pp.38-38
    • /
    • 2001
  • We cloned the cDNA encoding the neuron-specific $\beta$-subunit ($\beta$4) of large-conductance calcium-activated potassium channels from rat brain and determined the DNA sequences of the entire coding region (GenBank accession; AY028605). The deduced amino acid sequences of r$\beta$4, 210 amino acids in length, are closely related to the $BK_{Ca}$ $\beta$4 subunits of other species but show only limited sequence homology to other $\beta$-subunits, $\beta$1-$\beta$3.(omitted)d)

  • PDF

The Stress-Activated Signaling (SAS) Pathways of a Human Fungal Pathogen, Cryptococcus neoformans

  • Jung, Kwang-Woo;Bahn, Yong-Sun
    • Mycobiology
    • /
    • v.37 no.3
    • /
    • pp.161-170
    • /
    • 2009
  • Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC(protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The $Ca^{2+}$/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.

Loess and Lime Treatment for Modification of Waterworks Sludges (황토와 석회의 혼합처리에 의한 정수 슬러지의 개질화에 관한 연구)

  • Lim, Sung-Jin;Cho, Jae-Jun;Lee, Jae-Bok
    • Journal of Korean Society of Water and Wastewater
    • /
    • v.14 no.4
    • /
    • pp.318-327
    • /
    • 2000
  • Sludge production from water treatment plants is increasing each year because water resources deterioration is proceeding and water supply facilities are growing due to water demand increase. Water treatment plant sludges can be modified to soil cover in sanitary landfilling site through the lime treatment and other alternatives. The compression strength of $1.0kg/cm^2$ is necessary for the dozer operation on soft son cover material at municipal landfilling site. Modified sludge was experimentally produced in this study with lime, bentonite, loess, and activated loess dosing. X-ray diffraction patterns of the limed water treatment plant sludge confirmed the presence of calcium carbonate and ettringite. Unconfined compression strength properties of modified sludges showed material property improvement applicable for soil cover alternatives. When adding 20-30% activated loess to water treatment plant sludges. the modified sludges could reach the compression strength for cover soil after 7 days solidification reaction, but decrease of compression strength was intentioned in 28 days reaction period. Solidification effect of the modified sludge with activated loess was observed through the scanning electron microscope.

  • PDF