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https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#1
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...
December 27, 2016: 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27936394/increased-intracellular-ca-2-decreases-cisplatin-resistance-by-regulating-inos-expression-in-human-ovarian-cancer-cells
#12
Yang Yu, Qi Xie, Weimin Liu, Yuting Guo, Na Xu, Lu Xu, Shibing Liu, Songyan Li, Ye Xu, Liankun Sun
Previous studies have reported that intracellular Ca(2+) signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca(2+) and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDP(S)) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27887748/probes-for-manipulating-and-monitoring-ip3
#13
REVIEW
Akitoshi Miyamoto, Katsuhiko Mikoshiba
Inositol 1,4,5-trisphosphate (IP3) is an important second messenger produced via G-protein-coupled receptor- or receptor tyrosine kinase-mediated pathways. IP3 levels induce Ca(2+) release from the endoplasmic reticulum (ER) via IP3 receptor (IP3R) located in the ER membrane. The resultant spatiotemporal pattern of Ca(2+) signals regulates diverse cellular functions, including fertilization, gene expression, synaptic plasticity, and cell death. Therefore, monitoring and manipulating IP3 levels is important to elucidate not only the functions of IP3-mediated pathways but also the encoding mechanism of IP3R as a converter of intracellular signals from IP3 to Ca(2+)...
November 17, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27884701/cardiac-inositol-1-4-5-trisphosphate-receptors
#14
REVIEW
M Iveth Garcia, Darren Boehning
Calcium is a second messenger that regulates almost all cellular functions. In cardiomyocytes, calcium plays an integral role in many functions including muscle contraction, gene expression, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of calcium channels that are ubiquitously expressed in all tissues. In the heart, IP3Rs have been associated with regulation of cardiomyocyte function in response to a variety of neurohormonal agonists, including those implicated in cardiac disease...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27864646/low-level-laser-irradiation-modulates-brain-derived-neurotrophic-factor-mrna-transcription-through-calcium-dependent-activation-of-the-erk-creb-pathway
#15
Xiaodong Yan, Juanfang Liu, Zhengping Zhang, Wenhao Li, Siguo Sun, Jian Zhao, Xin Dong, Jixian Qian, Honghui Sun
Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca(2+) imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis...
January 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/27857196/step-activation-by-g%C3%AE-q-coupled-gpcrs-opposes-src-regulation-of-nmda-receptors-containing-the-glun2a-subunit
#16
Meng Tian, Jian Xu, Gang Lei, Paul J Lombroso, Michael F Jackson, John F MacDonald
N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27836216/regulation-of-ip3-receptors-by-cyclic-amp
#17
REVIEW
Colin W Taylor
Ca(2+) and cAMP are ubiquitous intracellular messengers and interactions between them are commonplace. Here the effects of cAMP on inositol 1,4,5-trisphosphate receptors (IP3Rs) are briefly reviewed. All three subtypes of IP3R are phosphorylated by cAMP-dependent protein kinase (PKA). This potentiates IP3-evoked Ca(2+) release through IP3R1 and IP3R2, but probably has little effect on IP3R3. In addition, cAMP can directly sensitize all three IP3R subtypes to IP3. The high concentrations of cAMP required for this PKA-independent modulation of IP3Rs is delivered to them within signalling junctions that include type 6 adenylyl cyclase and IP3R2...
November 6, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27777977/ip3-receptors-regulate-vascular-smooth-muscle-contractility-and-hypertension
#18
Qingsong Lin, Guiling Zhao, Xi Fang, Xiaohong Peng, Huayuan Tang, Hong Wang, Ran Jing, Jie Liu, W Jonathan Lederer, Ju Chen, Kunfu Ouyang
Inositol 1, 4, 5-trisphosphate receptor-mediated (IP3R-mediated) calcium (Ca(2+)) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle-specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca(2+) release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27771899/determining-the-roles-of-inositol-trisphosphate-receptors-in-neurodegeneration-interdisciplinary-perspectives-on-a-complex-topic
#19
Silvia Honda Takada, Juliane Midori Ikebara, Erica de Sousa, Débora Sterzeck Cardoso, Rodrigo Ribeiro Resende, Henning Ulrich, Martin Rückl, Sten Rüdiger, Alexandre Hiroaki Kihara
It is well known that calcium (Ca(2+)) is involved in the triggering of neuronal death. Ca(2+) cytosolic levels are regulated by Ca(2+) release from internal stores located in organelles, such as the endoplasmic reticulum. Indeed, Ca(2+) transit from distinct cell compartments follows complex dynamics that are mediated by specific receptors, notably inositol trisphosphate receptors (IP3Rs). Ca(2+) release by IP3Rs plays essential roles in several neurological disorders; however, details of these processes are poorly understood...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27749281/comparison-of-gating-dynamics-of-different-ip3r-channels-with-immune-algorithm-searching-for-channel-parameter-distributions
#20
Xiuhong Cai, Xiang Li, Hong Qi, Fang Wei, Jianyong Chen, Jianwei Shuai
The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca(2+) ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model...
October 17, 2016: Physical Biology
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