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https://www.readbyqxmd.com/read/29150934/the-current-status-and-perspectives-regarding-the-clinical-implication-of-intracellular-calcium-in-breast-cancer
#1
REVIEW
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca(2+) ) act as second messengers in intracellular signaling. Ca(2+) pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca(2+) as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca(2+) also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29141923/src-family-kinase-inhibitors-blunt-the-pacap-induced-pac1-receptor-endocytosis-phosphorylation-of-erk-and-increase-in-cardiac-neuron-excitability
#2
John D Tompkins, Todd A Clason, Thomas R Buttolph, Beatrice M Girard, Anne K Linden, Jean C Hardwick, Laura A Merriam, Victor May, Rodney L Parsons
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. However, additional mechanisms responsible for the enhanced excitability are activated following internalization of the PAC1 receptor and endosomal signaling. Src family kinases play critical roles mediating endocytosis of many trophic factor and G-protein coupled receptors...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29138405/ca-2-signals-initiate-at-immobile-ip3-receptors-adjacent-to-er-plasma-membrane-junctions
#3
Nagendra Babu Thillaiappan, Alap P Chavda, Stephen C Tovey, David L Prole, Colin W Taylor
IP3 receptors (IP3Rs) release Ca(2+) from the ER when they bind IP3 and Ca(2+). The spatial organization of IP3Rs determines both the propagation of Ca(2+) signals between IP3Rs and the selective regulation of cellular responses. Here we use gene editing to fluorescently tag endogenous IP3Rs, and super-resolution microscopy to determine the geography of IP3Rs and Ca(2+) signals within living cells. We show that native IP3Rs cluster within ER membranes. Most IP3R clusters are mobile, moved by diffusion and microtubule motors...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131545/a-double-point-mutation-at-residues-ile14-and-val15-of-bcl-2-uncovers-a-role-for-bh4-domain-in-both-protein-stability-and-function
#4
Giovanni Monaco, Rita La Rovere, Spyridoula Karamanou, Kirsten Welkenhuyzen, Hristina Ivanova, Elien Vandermarliere, Marta Di Martile, Donatella Del Bufalo, Humbert De Smedt, Jan B Parys, Anastassios Economou, Geert Bultynck
B-cell lymphoma 2 (Bcl-2) protein is the archetype apoptosis suppressor protein. The N-terminal Bcl-2-homology 4 (BH4) domain of Bcl-2 is required for the anti-apoptotic function of this protein at the mitochondria and endoplasmic reticulum (ER). The involvement of the BH4 domain in Bcl-2's anti-apoptotic functions has been proposed based on Gly-based substitutions of the Ile14/Val15 amino acids, two hydrophobic residues located in the centre of Bcl-2's BH4 domain. Following this strategy, we recently showed that a BH4-domain-derived peptide in which Ile14 and Val15 have been replaced by Gly residues, was unable to dampen pro-apoptotic Ca(2+) -release events from the ER...
November 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29131377/new-insights-of-subfertility-among-transplanted-women-immunosuppressive-drug-fk506-leads-to-calcium-leak-and-oocyte-activation-before-fertilization
#5
Linlin Liu, Man Yang, Naiqiang Wang, Li Li, Zi-Jiang Chen, Cong Zhang
FKBP12, known as FK506 binding protein, binds to immunosuppressive drug FK506, which must be taken by patients who received organ transplant. The side effect of FK506 is that women have difficulties in bearing a baby, so it is important to find the reason of their subfertility. This research explored the expression of FKBP12 in pre-implantation embryos and investigated its potential effect on reproduction. The results demonstrate that FKBP12 had good co-localization with endoplasmic reticulum and inositol-1, 4, 5- trisphosphate receptor in pre-implantation stages...
November 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29069790/downregulation-of-type-3-inositol-1-4-5-trisphosphate-receptor-decreases-breast-cancer-cell-migration-through-an-oscillatory-ca-2-signal
#6
Abdallah Mound, Alexia Vautrin-Glabik, Arthur Foulon, Béatrice Botia, Frédéric Hague, Jan B Parys, Halima Ouadid-Ahidouch, Lise Rodat-Despoix
Breast cancer remains a research priority due to its invasive phenotype. Although the role of ion channels in cancer is now well established, the role of inositol (1,4,5)-trisphosphate (IP3) receptors (IP3Rs) remains enigmatic. If the three IP3Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP3R type 3 (IP3R3) in the migration processes of three human breast cancer cell lines showing different migration velocities: the low-migrating MCF-7 and the highly migrating and invasive MDA-MB-231 and MDA-MB-435S cell lines...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29054453/disruption-of-dopamine-d1-d2-receptor-complex-is-involved-in-the-function-of-haloperidol-in-cardiac-h9c2-cells
#7
L Lencesova, I Szadvari, P Babula, J Kubickova, B Chovancova, K Lopusna, I Rezuchova, Z Novakova, O Krizanova, M Novakova
AIMS: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats...
October 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29048338/g-protein-dependent-signal-transduction-and-ubiquitination-in-dictyostelium
#8
REVIEW
Barbara Pergolizzi, Salvatore Bozzaro, Enrico Bracco
Signal transduction through G-protein-coupled receptors (GPCRs) is central for the regulation of virtually all cellular functions, and it has been widely implicated in human diseases. These receptors activate a common molecular switch that is represented by the heterotrimeric G-protein generating a number of second messengers (cAMP, cGMP, DAG, IP3, Ca(2+) etc.), leading to a plethora of diverse cellular responses. Spatiotemporal regulation of signals generated by a given GPCR is crucial for proper signalling and is accomplished by a series of biochemical modifications...
October 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29042668/signalling-mechanisms-in-paf-induced-intestinal-failure
#9
Ingmar Lautenschläger, Yuk Lung Wong, Jürgen Sarau, Torsten Goldmann, Karina Zitta, Martin Albrecht, Inéz Frerichs, Norbert Weiler, Stefan Uhlig
Capillary leakage syndrome, vasomotor disturbances and gut atony are common clinical problems in intensive care medicine. Various inflammatory mediators and signalling pathways are involved in these pathophysiological alterations among them platelet-activating factor (PAF). The related signalling mechanisms of the PAF-induced dysfunctions are only poorly understood. Here we used the model of the isolated perfused rat small intestine to analyse the role of calcium (using calcium deprivation, IP-receptor blockade (2-APB)), cAMP (PDE-inhibition plus AC activator), myosin light chain kinase (inhibitor ML-7) and Rho-kinase (inhibitor Y27632) in the following PAF-induced malfunctions: vasoconstriction, capillary and mucosal leakage, oedema formation, malabsorption and atony...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042597/herpud1-negatively-regulates-pathological-cardiac-hypertrophy-by-inducing-ip3-receptor-degradation
#10
Natalia Torrealba, Mario Navarro-Marquez, Valeria Garrido, Zully Pedrozo, Diego Romero, Yuka Eura, Elisa Villalobos, Juan Carlos Roa, Mario Chiong, Koichi Kokame, Sergio Lavandero
Cardiac hypertrophy is an adaptive response triggered by pathological stimuli. Regulation of the synthesis and the degradation of the Ca(2+) channel inositol 1,4,5-trisphosphate receptor (IP3R) affects progression to cardiac hypertrophy. Herpud1, a component of the endoplasmic reticulum-associated degradation (ERAD) complex, participates in IP3R1 degradation and Ca(2+) signaling, but the cardiac function of Herpud1 remains unknown. We hypothesize that Herpud1 acts as a negative regulator of cardiac hypertrophy by regulating IP3R protein levels...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29040664/coumestrol-induces-mitochondrial-dysfunction-by-stimulating-ros-production-and-calcium-ion-influx-into-mitochondria-in-human-placental-choriocarcinoma-cells
#11
Whasun Lim, Changwon Yang, Muhah Jeong, Fuller W Bazer, Gwonhwa Song
STUDY QUESTION: Does coumestrol inhibit proliferation of human placental choriocarcinoma cells? SUMMARY ANSWER: Coumestrol promotes cell death in the choriocarcinoma cells by regulating ERK1/2 MAPK and JNK MAPK signaling pathways and through disruption of Ca2+ and ROS homeostasis. WHAT IS KNOWN ALREADY: A number of patients who suffer from choriocarcinomas fail to survive due to delayed diagnosis or a recurrent tumor and resistance to traditional chemotherapy using platinum-based agents and methotrexate...
November 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#12
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29029792/analyzing-optical-imaging-of-ca-2-signals-via-tirf-microscopy-the-limits-on-resolution-due-to-chemical-rates-and-depth-of-the-channels
#13
Patrick Toglia, Ghanim Ullah, John E Pearson
High resolution total internal reflection (TIRF) microscopy (TIRFM) together with detailed computational modeling provides a powerful approach towards the understanding of a wide range of Ca(2+) signals mediated by the ubiquitous inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) channel. Exploiting this fruitful collaboration further requires close agreement between the models and observations. However, elementary Ca(2+) release events, puffs, imaged through TIRFM do not show the rapid single-channel openings and closings during and between puffs as are present in simulated puffs using data-driven single channel models...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29024661/paclitaxel-reduces-axonal-bclw-to-initiate-ip3r1-dependent-axon-degeneration
#14
Sarah E Pease-Raissi, Maria F Pazyra-Murphy, Yihang Li, Franziska Wachter, Yusuke Fukuda, Sara J Fenstermacher, Lauren A Barclay, Gregory H Bird, Loren D Walensky, Rosalind A Segal
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of many cancer treatments. The hallmark of CIPN is degeneration of long axons required for transmission of sensory information; axonal degeneration causes impaired tactile sensation and persistent pain. Currently the molecular mechanisms of CIPN are not understood, and there are no available treatments. Here we show that the chemotherapeutic agent paclitaxel triggers CIPN by altering IP3 receptor phosphorylation and intracellular calcium flux, and activating calcium-dependent calpain proteases...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/28993769/phosphoproteomics-reveals-regulatory-t-cell-mediated-def6-dephosphorylation-that-affects-cytokine-expression-in-human-conventional-t-cells
#15
Rubin N Joshi, Nadine A Binai, Francesco Marabita, Zhenhua Sui, Amnon Altman, Albert J R Heck, Jesper Tegnér, Angelika Schmidt
Regulatory T cells (Tregs) control key events of immune tolerance, primarily by suppression of effector T cells. We previously revealed that Tregs rapidly suppress T cell receptor (TCR)-induced calcium store depletion in conventional CD4(+)CD25(-) T cells (Tcons) independently of IP3 levels, consequently inhibiting NFAT signaling and effector cytokine expression. Here, we study Treg suppression mechanisms through unbiased phosphoproteomics of primary human Tcons upon TCR stimulation and Treg-mediated suppression, respectively...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28981616/spreading-depression-promotes-astrocytic-calcium-oscillations-and-enhances-gliotransmission-to-hippocampal-neurons
#16
Dong Chuan Wu, Rita Yu-Tzu Chen, Ting-Chun Cheng, Yao-Chang Chiang, Mei-Lin Shen, Li-Ling Hsu, Ning Zhou
Spreading depression (SD) is a pathophysiological phenomenon characterized by propagating waves of profound neuronal and glial depolarization in central nervous system gray matter. Although SD is primarily mediated by neurons with a subsequent astrocytic response, it remains unclear how astrocytic activity is modulated after SD and how altered astrocyte signaling contribute to neuronal excitability. Here, we report that after the concurrent Ca2+ wave, SD enhanced astrocytic activity by promoting a secondary period of Ca2+ oscillations...
August 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28980722/calcium-signaling-of-in-situ-chondrocytes-in-articular-cartilage-under-compressive-loading-roles-of-calcium-sources-and-cell-membrane-ion-channels
#17
Mengxi Lv, Yilu Zhou, Xingyu Chen, Lin Han, Liyun Wang, X Lucas Lu
Mechanical loading on articular cartilage can induce many physical and chemical stimuli on chondrocytes residing in the extracellular matrix (ECM). Intracellular calcium ([Ca(2+) ]i ) signaling is among the earliest responses of chondrocytes to physical stimuli, but the [Ca(2+) ]i signaling of in situ chondrocytes in loaded cartilage is not fully understood due to the technical challenges in [Ca(2+) ]i imaging of chondrocytes in a deforming ECM. This study developed a novel bi-directional microscopy loading device that enables the record of transient [Ca(2+) ]i responses of in situ chondrocytes in loaded cartilage...
October 5, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28974495/prenatal-hypoxia-induced-dysfunction-in-cerebral-arteries-of-offspring-rats
#18
Jiaqi Tang, Na Li, Xueyi Chen, Qinqin Gao, Xiuwen Zhou, Yingying Zhang, Bailin Liu, Miao Sun, Zhice Xu
BACKGROUND: Hypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults. This study determined angiotensin II (AII)-mediated vascular dysfunction in offspring middle cerebral arteries (MCA). METHODS AND RESULTS: Pregnant rats were subjected to hypoxia. Vascular tension in offspring MCA by AII with or without inhibitors, calcium channel activities, and endoplasmic reticulum calcium stores were tested. Whole-cell patch clamping was used to investigate voltage-dependent calcium channel currents...
October 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28949794/control-of-protein-translation-by-ip3r-mediated-ca-2-release-in-drosophila-neuroendocrine-cells
#19
Gaiti Hasan
The inositol 1,4,5-trisphosphate receptor (IP3R) is one of two Ca(2+) channels that gates Ca(2+) release from ER-stores. The ligand IP3, generated upon specific G-protein coupled receptor activation, binds to IP3R to release Ca(2+) into the cytosol. IP3R also mediates ER-store Ca(2+) release into the mitochondria, under basal as well as stimulatory conditions; an activity that influences cellular bioenergetics and thus, cellular growth and proliferation. In Drosophila neuroendocrine cells expressing a hypomorphic mutant of IP3R, we observed reduced protein translation levels...
September 26, 2017: Fly
https://www.readbyqxmd.com/read/28942449/fshr-and-lhr-expression-and-signaling-as-well-as-maturation-and-apoptosis-of-cumulus-oocyte-complexes-following-treatment-with-fsh-receptor-binding-inhibitor-in-sheep
#20
Suocheng Wei, Xiaoyun Shen, Zhuandi Gong, Yingying Deng, Luju Lai, Haoqin Liang
BACKGROUND/AIMS: Currently, it remains unknown whether FSH receptor binding inhibitor (FRBI) influences follicular development and reproduction functions in humans and animals. The present study aimed to investigate FRBI effects on in vitro maturation (IVM) and apoptosis of cumulus-oocyte complexes (COCs) of sheep, to determine the effect of FRBI on mRNA and protein levels of FSHR and LHR in COCs, and to elucidate the signal pathway of FRBI effects. METHODS: COCs were in vitro cultured for 24h in the IVM media supplemented with varying concentrations of FRBI (0, 10, 20, 30 and 40µg/mL) and FSH (10IU/mL)...
2017: Cellular Physiology and Biochemistry
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