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https://www.readbyqxmd.com/read/28196740/dpb162-ae-an-inhibitor-of-store-operated-ca-2-entry-can-deplete-the-endoplasmic-reticulum-ca-2-store
#1
Mart Bittremieux, Julia V Gerasimenko, Marleen Schuermans, Tomas Luyten, Eloise Stapleton, Kamil J Alzayady, Humbert De Smedt, David I Yule, Katsuhiko Mikoshiba, Peter Vangheluwe, Oleg V Gerasimenko, Jan B Parys, Geert Bultynck
Store-operated Ca(2+) entry (SOCE), an important Ca(2+) signaling pathway in non-excitable cells, regulates a variety of cellular functions. To study its physiological role, pharmacological tools, like 2-aminoethyl diphenylborinate (2-APB), are used to impact SOCE. 2-APB is one of the best characterized SOCE inhibitors. However, 2-APB also activates SOCE at lower concentrations, while it inhibits inositol 1,4,5-trisphosphate receptors (IP3Rs), sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs) and other ion channels, like TRP channels...
February 1, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28183802/differential-effects-of-anoctamins-on-intracellular-calcium-signals
#2
Inês Cabrita, Roberta Benedetto, Ana Fonseca, Podchanart Wanitchakool, Lalida Sirianant, Boris V Skryabin, Laura K Schenk, Hermann Pavenstädt, Rainer Schreiber, Karl Kunzelmann
The Ca(2+) activated Cl(-) channel TMEM16A [anoctamin (ANO)1] is homologous to yeast Ist2 and has been shown to tether the cortical endoplasmic reticulum (ER) to the plasma membrane. We therefore examined whether ANO1 and other members of the ANO family affect intracellular Ca(2+) ([Ca(2+)]i) signals. It is shown that expression of ANO1 augments Ca(2+) store release upon stimulation of GPCRs, whereas knockdown of ANO1, or lack of Ano1 expression in Ano1(-/-) animals as shown in an earlier report, inhibits Ca(2+) release...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#3
Zeting Yuan, Aili Cao, Hua Liu, Henjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28179072/orai3-channel-is-the-2-apb-induced-endoplasmic-reticulum-calcium-leak
#4
Daniel Leon-Aparicio, Jonathan Pacheco, Jesus Chavez-Reyes, Jose M Galindo, Jesus Valdes, Luis Vaca, Agustin Guerrero-Hernandez
We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca(2+) leak using synthetic Ca(2+) indicators that report changes in both the cytoplasmic ([Ca(2+)]i) and the luminal ER ([Ca(2+)]ER) Ca(2+) concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca(2+) leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca(2+)]ER but did not decrease the ER Ca(2+) leak after thapsigargin (TG)...
January 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28179071/the-bh4-domain-of-bcl-2-orthologues-from-different-classes-of-vertebrates-can-act-as-an-evolutionary-conserved-inhibitor-of-ip3-receptor-channels
#5
Hristina Ivanova, Tomas Luyten, Elke Decrock, Tim Vervliet, Luc Leybaert, Jan B Parys, Geert Bultynck
Ca(2+) signalling plays an important role in various physiological processes in vertebrates. In mammals, the highly conserved anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein is an important modulator of the inositol 1,4,5-trisphosphate receptor (IP3R), i.e. the main intracellular Ca(2+) - release channel located at the endoplasmic reticulum (ER). The Bcl-2 Homology (BH) 4 domain of Bcl-2 (BH4-Bcl-2) is a critical determinant for inhibiting IP3Rs, by directly targeting a region in the modulatory domain of the receptor (domain 3)...
January 25, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28130333/can-endothelial-hemoglobin-alpha-regulate-nitric-oxide-vasodilatory-signaling
#6
Jaimit Parikh, Adam Kapela, Nikolaos M Tsoukias
We utilized mathematical modeling to investigate nitric oxide (NO)-dependent vasodilatory signaling in the arteriolar wall. Detailed continuum cellular models of calcium (Ca(2+)) dynamics and membrane electrophysiology in smooth muscle (SMC) and endothelial cells (EC) were coupled with models of NO signaling and biotransport in an arteriole. We use this theoretical approach to examine the role of endothelial hemoglobin alpha (Hbα) as a modulator of NO-mediated myoendothelial feedback as previously suggested in Straub al...
January 27, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28122214/importance-of-altered-levels-of-serca-ip3r-and-ryr-in-vascular-smooth-muscle-cell
#7
Jaijus Pallippadan Johny, Michael J Plank, Tim David
Calcium cycling between the sarcoplasmic reticulum (SR) and the cytosol via the sarco-/endoplasmic reticulum Ca-ATPase (SERCA) pump, inositol-1,4,5-triphosphate receptor (IP3R), and Ryanodine receptor (RyR), plays a major role in agonist-induced intracellular calcium ([Ca(2+)]cyt) dynamics in vascular smooth muscle cells (VSMC). Levels of these calcium handling proteins in SR get altered under disease conditions. We have developed a mathematical model to understand the significance of altered levels of SERCA, IP3R, and RyR on the intracellular calcium dynamics of VSMC and to understand how variation in protein levels that arise due to diabetes contribute to different VSMC behavior and thus vascular disease...
January 24, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28108028/comparison-of-ca-2-puffs-evoked-by-extracellular-agonists-and-photoreleased-ip3
#8
Jeffrey T Lock, Ian F Smith, Ian Parker
The inositol trisphosphate (IP3) signaling pathway evokes local Ca(2+) signals (Ca(2+) puffs) that arise from the concerted openings of clustered IP3 receptor/channels in the ER membrane. Physiological activation is triggered by binding of agonists to G-protein-coupled receptors (GPCRs) on the cell surface, leading to cleavage of phosphatidyl inositol bisphosphate and release of IP3 into the cytosol. Photorelease of IP3 from a caged precursor provides a convenient and widely employed means to study the final stage of IP3-mediated Ca(2+) liberation, bypassing upstream signaling events to enable more precise control of the timing and relative concentration of cytosolic IP3...
December 5, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28105751/stim-1-and-orai-1-channel-mediate-angiotensin-ii-induced-expression-of-egr-1-in-vascular-smooth-muscle-cells
#9
Estelle R Simo-Cheyou, Ju Jing Tan, Ryszard Grygorczyk, Ashok K Srivastava
An upregulation of Egr-1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr-1 in vascular smooth muscle cells (VSMC). Angiotensin-II (Ang-II) is a key vasoactive peptide that has been implicated in the pathogenesis of vascular diseases. Ang-II elevates intracellular Ca(2+) through activation of the store-operated calcium entry (SOCE) involving an inositol-3-phosphate receptor (IP3R)-coupled depletion of endoplasmic reticular Ca(2+) and a subsequent activation of the stromal interaction molecule 1 (STIM-1) /Orai-1 complex...
January 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#10
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28072885/functional-role-of-intracellular-calcium-receptor-inositol-1-4-5-trisphosphate-type-1-in-rat-hippocampus-after-neonatal-anoxia
#11
Juliane Midori Ikebara, Silvia Honda Takada, Débora Sterzeck Cardoso, Natália Myuki Moralles Dias, Beatriz Crossiol Vicente de Campos, Talitha Amanda Sanches Bretherick, Guilherme Shigueto Vilar Higa, Mariana Sacrini Ayres Ferraz, Alexandre Hiroaki Kihara
Anoxia is one of the most prevalent causes of neonatal morbidity and mortality, especially in preterm neonates, constituting an important public health problem due to permanent neurological sequelae observed in patients. Oxygen deprivation triggers a series of simultaneous cascades, culminating in cell death mainly located in more vulnerable metabolic brain regions, such as the hippocampus. In the process of cell death by oxygen deprivation, cytosolic calcium plays crucial roles. Intracellular inositol 1,4,5-trisphosphate receptors (IP3Rs) are important regulators of cytosolic calcium levels, although the role of these receptors in neonatal anoxia is completely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28072864/1h-nmr-metabolomics-reveals-association-of-high-expression-of-inositol-1-4-5-trisphosphate-receptor-and-metabolites-in-breast-cancer-patients
#12
Aru Singh, Raj Kumar Sharma, Megha Chagtoo, Gaurav Agarwal, Nelson George, Neeraj Sinha, Madan M Godbole
1H NMR is used to detect alterations in metabolites and their linkage to metabolic processes in a number of pathological conditions including breast cancer. Inositol 1, 4, 5 trisphosphate (IP3R) receptor is an intracellular calcium channel known to regulate metabolism and cellular bioenergetics. Its expression is up regulated in a number of cancers. However, its linkage to metabolism in disease conditions has not been evaluated. This study was designed to determine the association if any, of these metabolites with altered expression of IP3R in breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28066549/synthesis-of-dimeric-analogs-of-adenophostin-a-that-potently-evoke-ca-2-release-through-ip3-receptors
#13
Amol M Vibhute, Poornenth Pushpanandan, Maria Varghese, Vera Koniecnzy, Colin W Taylor, Kana M Sureshan
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are tetrameric intracellular channels through which many extracellular stimuli initiate the Ca(2+) signals that regulate diverse cellular responses. There is considerable interest in developing novel ligands of IP3R. Adenophostin A (AdA) is a potent agonist of IP3R and since some dimeric analogs of IP3R ligands are more potent than the corresponding monomer; we considered whether dimeric AdA analogs might provide agonists with increased potency. We previously synthesized traizolophostin, in which a simple triazole replaced the adenine of AdA, and showed it to be equipotent to AdA...
November 3, 2016: RSC Advances
https://www.readbyqxmd.com/read/28062709/trifluoperazine-a-well-known-antipsychotic-inhibits-glioblastoma-invasion-by-binding-to-calmodulin-and-disinhibiting-calcium-release-channel-ip3r
#14
Seokmin Kang, Jinpyo Hong, Jung Moo Lee, Hyo Eun Moon, Borami Jeon, Jungil Choi, Nal Ae Yoon, Sun Ha Paek, Eun Joo Roh, C Justin Lee, Sang Soo Kang
Calcium (Ca(2+)) signaling is an important signaling process, implicated in cancer cell proliferation and motility of the deadly glioblastomas that aggressively invade neighboring brain tissue. We have previously demonstrated that caffeine blocks glioblastoma invasion and extends survival by inhibiting Ca(2+) release channel inositol 1,4,5-trisphosphate receptor (IP3R) subtype 3. Trifluoperazine (TFP) is an FDA-approved antipsychotic drug for schizophrenia. Interestingly, TFP has been recently reported to show a strong anticancer effect on lung cancer, hepatocellular carcinoma, and T-cell lymphoma...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28060261/study-of-endoplasmic-reticulum-and-mitochondria-interactions-by-in-situ-proximity-ligation-assay-in-fixed-cells
#15
Emily Tubbs, Jennifer Rieusset
Structural interactions between the endoplasmic reticular (ER) and mitochondrial membranes, in domains known as mitochondria-associated membranes (MAM), are crucial hubs for cellular signaling and cell fate. Particularly, these inter-organelle contact sites allow the transfer of calcium from the ER to mitochondria through the voltage-dependent anion channel (VDAC)/glucose-regulated protein 75 (GRP75)/inositol 1,4,5-triphosphate receptor (IP3R) calcium channeling complex. While this subcellular compartment is under intense investigation in both physiological and pathological conditions, no simple and sensitive method exists to quantify the endogenous amount of ER-mitochondria contact in cells...
December 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28012441/ugonin-u-stimulates-nlrp3-inflammasome-activation-and-enhances-inflammasome-mediated-pathogen-clearance
#16
Chun-Yu Chen, Chuan-Hui Yang, Yung-Fong Tsai, Chih-Chuang Liaw, Wen-Yi Chang, Tsong-Long Hwang
The NOD-like receptor pyrin domain 3 (NLRP3) inflammasome contains Nod-like receptors, a subclass of pattern recognition receptors, suggesting that this complex has a prominent role in host defenses. Various structurally diverse stimulators activate the NLRP3 inflammasome through different signaling pathways. We previously reported that ugonin U (UgU), a natural flavonoid isolated from Helminthostachys zeylanica (L) Hook, directly stimulates phospholipase C (PLC) and triggers superoxide release in human neutrophils...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/27995898/irbit-controls-apoptosis-by-interacting-with-the-bcl-2-homolog-bcl2l10-and-by-promoting-er-mitochondria-contact
#17
Benjamin Bonneau, Hideaki Ando, Katsuhiro Kawaai, Matsumi Hirose, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba
IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca(2+) transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca(2+) release through IP3R in mitochondria induces cell death...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27979909/distinct-cellular-states-determine-calcium-signaling%C3%A2-response
#18
Jason Yao, Anna Pilko, Roy Wollman
The heterogeneity in mammalian cells signaling response is largely a result of pre-existing cell-to-cell variability. It is unknown whether cell-to-cell variability rises from biochemical stochastic fluctuations or distinct cellular states. Here, we utilize calcium response to adenosine trisphosphate as a model for investigating the structure of heterogeneity within a population of cells and analyze whether distinct cellular response states coexist. We use a functional definition of cellular state that is based on a mechanistic dynamical systems model of calcium signaling...
December 15, 2016: Molecular Systems Biology
https://www.readbyqxmd.com/read/27975174/dysregulation-of-intracellular-ca-2-in-dystrophic-cortical-and-hippocampal-neurons
#19
José R Lopez, Juan Kolster, Arkady Uryash, Eric Estève, Francisco Altamirano, José A Adams
Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder characterized by skeletal muscle wasting, cardiomyopathy, as well as cognitive impairment. Lack of dystrophin in striated muscle produces dyshomeostasis of resting intracellular Ca(2+) ([Ca(2+)]i), Na(+) ([Na(+)]i), and oxidative stress. Here, we test the hypothesis that similar to striated muscle cells, an absence of dystrophin in neurons from mdx mice (a mouse model for DMD) is also associated with dysfunction of [Ca(2+)]i homeostasis and oxidative stress...
December 15, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27941214/calcium-alterations-signal-either-to-senescence-or-to-autophagy-induction-in-stem-cells-upon-oxidative-stress
#20
Aleksandra V Borodkina, Alla N Shatrova, Pavel I Deryabin, Anastasiia A Griukova, Polina A Abushik, Sergei M Antonov, Nikolay N Nikolsky, Elena B Burova
Intracellular calcium ([Ca(2+)]i) has been reported to play an important role in autophagy, apoptosis and necrosis, however, a little is known about its impact in senescence. Here we investigated [Ca(2+)]i contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal H2O2-treatment resulted in a rapid calcium release from intracellular stores mediated by the activation of PLC/IP3/IP3R pathway. Notably, further senescence development was accompanied by persistently elevated [Ca(2+)]i levels...
December 8, 2016: Aging
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