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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/29136773/the-potential-use-of-melatonin-to-treat-protozoan-parasitic-infections-a-review
#4
REVIEW
Ahmad Daryani, Mahbobeh Montazeri, Abdol Satar Pagheh, Mehdi Sharif, Shahabeddin Sarvi, Azam Hosseinzadeh, Russel J Reiter, Ramtin Hadighi, Mohammad Taghi Joghataei, Habib Ghaznavi, Saeed Mehrzadi
Melatonin (N-acetyl-5-methoxytryptamine) is a circadian hormone produced in vertebrates by the pineal gland and other organs. Melatonin is believed to influence immune cells leading to modulation of the proliferative response of stimulated lymphocytes as well as cytokine production. Due to the antioxidant and immunomodulatory effects of melatonin, it is suggested that this molecule could be a therapeutic alternative agent to fight bacterial, viral, and parasitic infections by a variety of mechanisms. Herein, we review the effects of melatonin on the cell biology of protozoan parasites and host's immune response...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#5
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
#6
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/29122926/defect-in-phosphoinositide-signalling-through-a-homozygous-variant-in-plcb3-causes-a-new-form-of-spondylometaphyseal-dysplasia-with-corneal-dystrophy
#7
Salma Ben-Salem, Sarah M Robbins, Nara Lm Sobreira, Angeline Lyon, Aisha M Al-Shamsi, Barira K Islam, Nadia A Akawi, Anne John, Pramathan Thachillath, Sania Al Hamed, David Valle, Bassam R Ali, Lihadh Al-Gazali
BACKGROUND: Bone dysplasias are a large group of disorders affecting the growth and structure of the skeletal system. METHODS: In the present study, we report the clinical and molecular delineation of a new form of syndromic autosomal recessive spondylometaphyseal dysplasia (SMD) in two Emirati first cousins. They displayed postnatal growth deficiency causing profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding and intellectual disability...
November 9, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29115528/plcd3-a-flotillin2-interacting-protein-is-involved-in-proliferation-migration-and-invasion-of-nasopharyngeal-carcinoma-cells
#8
Weidong Liu, Xuxu Liu, Lei Wang, Bin Zhu, Chang Zhang, Wei Jia, Hecheng Zhu, Xingdong Liu, Meizuo Zhong, Dan Xie, Yanyu Liu, Shasha Li, Jia Shi, Jianxing Lin, Xiaomeng Xia, Xingjun Jiang, Caiping Ren
Phospholipase C (PLC) is a pivotal enzyme in the phosphoinositide pathway that promotes the second messengers, diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), to participate in eukaryotic signal transduction. Several PLC isozymes are associated with cancer, such as PLC-β1, PLC-δ1, PLC-ε and PLC-γ1. However, the role of PLC-δ3 (PLCD3) in nasopharyngeal carcinoma (NPC) has not been investigated to date. In our previous study, we demonstrated that flotillin2 (Flot2) plays a pro-neoplastic role in NPC and is involved in tumour progression and metastasis...
November 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29109680/diversity-of-evoked-astrocyte-ca-2-dynamics-quantified-through-experimental-measurements-and-mathematical-modeling
#9
Marsa Taheri, Gregory Handy, Alla Borisyuk, John A White
Astrocytes are a major cell type in the mammalian brain. They are not electrically excitable, but generate prominent Ca(2+) signals related to a wide variety of critical functions. The mechanisms driving these Ca(2+) events remain incompletely understood. In this study, we integrate Ca(2+) imaging, quantitative data analysis, and mechanistic computational modeling to study the spatial and temporal heterogeneity of cortical astrocyte Ca(2+) transients evoked by focal application of ATP in mouse brain slices...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/29077882/cx32-hemichannel-opening-by-cytosolic-ca2-is-inhibited-by-the-r220x-mutation-that-causes-charcot-marie-tooth-disease
#10
Andrea Carrer, Alessandro Leparulo, Giulia Crispino, Catalin Dacian Ciubotaru, Oriano Marin, Francesco Zonta, Mario Bortolozzi
Mutations of the GJB1 gene encoding connexin 32 (Cx32) cause the X-linked form of Charcot-Marie-Tooth disease (CMTX1), a demyelinating peripheral neuropathy for which there is no cure. A growing body of evidence indicates that ATP release through Cx32 hemichannels in Schwann cells could be critical for nerve myelination, but it is unknown if CMTX1 mutations alter the cytosolic Ca2+-dependent gating mechanism that controls Cx32 hemichannel opening and ATP release. The current study uncovered that loss of the C-terminus in Cx32 (R220X mutation), which causes a severe CMTX1 phenotype, inhibits hemichannel opening during a canonical IP3-mediated increase in cytosolic Ca2+ in HeLa cells...
October 25, 2017: Human Molecular Genetics
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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/29029384/p53-upregulates-plc%C3%AE%C2%B5-ip3-ca-2-pathway-and-inhibits-autophagy-through-its-target-gene-rap2b
#19
Jiehui Di, Juanjuan Tang, Heya Qian, Derek A Franklin, Chad Deisenroth, Yoko Itahana, Junnian Zheng, Yanping Zhang
The tumor suppressor p53 plays a pivotal role in numerous cellular responses as it regulates cell proliferation, metabolism, cellular growth, and autophagy. In order to identify novel p53 target genes, we utilized an unbiased microarray approach and identified Rap2B as a robust candidate, which belongs to the Ras-related GTP-binding protein superfamily and exhibits increased expression in various human cancers. We demonstrated that p53 increases the intracellular IP3 and Ca(2+) levels and decreases the LC3 protein levels through its target gene Rap2B, suggesting that p53 can inhibit the autophagic response triggered by starvation via upregulation of the Rap2B-PLCε-IP3-Ca(2+) pathway...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29024661/paclitaxel-reduces-axonal-bclw-to-initiate-ip3r1-dependent-axon-degeneration
#20
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
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