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https://www.readbyqxmd.com/read/29688621/an-epigenetic-signature-in-adipose-tissue-is-linked-to-nicotinamide-n-methyltransferase-gene-expression
#1
Ana B Crujeiras, Pavlos Pissios, Jose M Moreno-Navarrete, Angel Diaz-Lagares, Juan Sandoval, Antonio Gomez, Wilfredo Ricart, Manel Esteller, Felipe F Casanueva, Jose M Fernandez-Real
SCOPE: The enzyme nicotinamide N-methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue. METHODS AND RESULTS: The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium HumanMethylation450 BeadChip array (discovery cohort: n  =  11). The findings were confirmed in two additional independent cohorts (Cohort 1: n  =  60; BMI 20-60 kg/m2 and cohort 2: n  =  40; BMI >40 kg/m2 ) and validated after weight loss (using microarray data)...
April 24, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29626493/profiling-calcium-signals-of-in-vitro-polarized-human-effector-cd4-t-cells
#2
Sarah Kircher, Maylin Merino-Wong, Barbara A Niemeyer, Dalia Alansary
Differentiation of naïve CD4+ T cells into effector subtypes with distinct cytokine profiles and physiological roles is a tightly regulated process, the imbalance of which can lead to an inadequate immune response or autoimmune disease. The crucial role of Ca2+ signals, mainly mediated by the store operated Ca2+ entry (SOCE) in shaping the immune response is well described. However, it is unclear if human effector CD4+ T cell subsets show differential Ca2+ signatures in response to different stimulation methods...
April 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29604961/deletion-of-orai2-augments-endogenous-crac-currents-and-degranulation-in-mast-cells-leading-to-enhanced-anaphylaxis
#3
Volodymyr Tsvilovskyy, Alejandra Solís-López, Dagmar Schumacher, Rebekka Medert, Axel Roers, Ulrich Kriebs, Marc Freichel
All three members of the Orai family of cation channels-Orai1, Orai2 and Orai3-are integral membrane proteins that can form store-operated Ca2+ channels resembling endogenous calcium release-activated channels (CRAC) in many aspects. Loss of function studies in human and murine models revealed many functions of Orai1 proteins not only for Ca2+ homeostasis, but also for cellular and systemic functions in many cell types. By contrast, the knowledge regarding the contribution of Orai2 and Orai3 proteins in these processes is sparse...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29480205/inhibition-of-trpc1-dependent-store-operated-calcium-entry-improves-synaptic-stability-and-motor-performance-in-a-mouse-model-of-huntington-s-disease
#4
Jun Wu, Daniel Ryskamp, Lutz Birnbaumer, Ilya Bezprozvanny
BACKGROUND: Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry. We previously demonstrated that supranormal nSOC leads to synaptic loss in striatal medium spiny neurons (MSNs) in YAC128 HD mice...
2018: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/29372030/changes-in-expression-of-klotho-affect-physiological-processes-diseases-and-cancer
#5
REVIEW
Nguyen Thi Xuan, Nong Van Hai
Klotho (KL) encodes a single-pass transmembrane protein and is predominantly expressed in the kidney, parathyroid glands, and choroid plexus. Genetic studies on the KL gene have revealed that DNA hypermethylation is one of the major risk factors for aging, diseases, and cancer. Besides, KL exerts anti-inflammatory and anti-tumor effects by regulating signaling pathways and the expression of target genes. KL participates in modulation of the insulin/insulin-like growth factor-1 (IGF-1) signaling, which induces the growth hormone (GH) secretion...
January 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29351410/hypoxia-selectively-upregulates-cation-channels-and-increases-cytosolic-ca-2-in-pulmonary-but-not-coronary-arterial-smooth-muscle-cells
#6
Xi He, Shanshan Song, Ramon J Ayon, Angela Balisterieri, Stephen M Black, Ayako Makino, W Gil Wier, Wei-Jin Zang, Jason X-J Yuan
Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE), plays a critical role in the development of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension. This study aimed to test the hypothesis that chronic hypoxia differentially regulates the expression of proteins that mediate SOCE and ROCE [stromal interacting molecule (STIM), Orai, and canonical transient receptor potential channel TRPC6] in pulmonary (PASMC) and coronary (CASMC) artery smooth muscle cells...
April 1, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29188077/orai1-2-3-and-stim1-promote-store-operated-calcium-entry-in-pulmonary-arterial-smooth-muscle-cells
#7
Jian Wang, Chuyi Xu, Qiuyu Zheng, Kai Yang, Ning Lai, Tao Wang, Haiyang Tang, Wenju Lu
Previous studies have demonstrated that besides the classic canonical transient receptor potential channel family, Orai family and stromal interaction molecule 1 (STIM1) might also be involved in the regulation of store-operated calcium channels (SOCCs). An increase in cytosolic free Ca2+ concentration promoted by store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation and migration of PASMCs. In this study, our data revealed the following: (1) in both rat distal pulmonary arteries and PASMCs, chronic hypoxia exposure upregulated the expression of Orai1 and Orai2, without affecting Orai3 and STIM1; (2) either heterozygous knockout of HIF-1 α in mice or knockdown of HIF-1 α in PASMCs abolished the hypoxic upregulation of Orai2, but not Orai1, suggesting the hypoxic upregulation of Orai2 depends on HIF-1 α ; and (3) using small interference RNA knockdown strategies, Orai1, 2, 3 and STIM1 were all shown to mediate SOCE in hypoxic PASMCs...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29155098/orai1-mutations-abolishing-store-operated-ca-2-entry-cause-anhidrotic-ectodermal-dysplasia-with-immunodeficiency
#8
Jayson Lian, Mario Cuk, Sascha Kahlfuss, Lina Kozhaya, Martin Vaeth, Frédéric Rieux-Laucat, Capucine Picard, Melina J Benson, Antonia Jakovcevic, Karmen Bilic, Iva Martinac, Peter Stathopulos, Imre Kacskovics, Thomas Vraetz, Carsten Speckmann, Stephan Ehl, Thomas Issekutz, Derya Unutmaz, Stefan Feske
BACKGROUND: Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ channels is an essential signaling pathway in many cell types. Ca2+ release-activated Ca2+ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and nonimmunologic symptoms. OBJECTIVE: We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology...
November 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28807148/acetylcholine-induces-intracellular-ca-2-oscillations-and-nitric-oxide-release-in-mouse-brain-endothelial-cells
#9
Estella Zuccolo, Dmitry Lim, Dlzar Ali Kheder, Angelica Perna, Paolo Catarsi, Laura Botta, Vittorio Rosti, Laura Riboni, Giulio Sancini, Franco Tanzi, Egidio D'Angelo, Germano Guerra, Francesco Moccia
Basal forebrain neurons increase cortical blood flow by releasing acetylcholine (Ach), which stimulates endothelial cells (ECs) to produce the vasodilating gasotransmitter, nitric oxide (NO). Surprisingly, the mechanism whereby Ach induces NO synthesis in brain microvascular ECs is unknown. An increase in intracellular Ca(2+) concentration recruits a multitude of endothelial Ca(2+)-dependent pathways, such as Ca(2+)/calmodulin endothelial NO synthase (eNOS). The present investigation sought to investigate the role of intracellular Ca(2+) signaling in Ach-induced NO production in bEND5 cells, an established model of mouse brain microvascular ECs, by conventional imaging of cells loaded with the Ca(2+)-sensitive dye, Fura-2/AM, and the NO-sensitive fluorophore, DAF-DM diacetate...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28446591/nfat5-sensitive-orai1-expression-and-store-operated-ca-2-entry-in-megakaryocytes
#10
Itishri Sahu, Lisann Pelzl, Basma Sukkar, Hajar Fakhri, Tamer Al-Maghout, Hang Cao, Stefan Hauser, Ravi Gutti, Meinrad Gawaz, Florian Lang
The transcription factor nuclear factor of activated T cells 5 (NFAT5) is up-regulated in several clinical disorders, including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase 1 (SGK1). The kinase is a powerful regulator of Orai1, a Ca2+ channel accomplishing store-operated Ca2+ entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca2+ sensors stromal interaction molecule 1 (STIM1), or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca2+ signaling in megakaryocytes...
August 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28294127/orai2-modulates-store-operated-calcium-entry-and-t-cell-mediated-immunity
#11
Martin Vaeth, Jun Yang, Megumi Yamashita, Isabelle Zee, Miriam Eckstein, Camille Knosp, Ulrike Kaufmann, Peter Karoly Jani, Rodrigo S Lacruz, Veit Flockerzi, Imre Kacskovics, Murali Prakriya, Stefan Feske
Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels is critical for lymphocyte function and immune responses. CRAC channels are hexamers of ORAI proteins that form the channel pore, but the contributions of individual ORAI homologues to CRAC channel function are not well understood. Here we show that deletion of Orai1 reduces, whereas deletion of Orai2 increases, SOCE in mouse T cells. These distinct effects are due to the ability of ORAI2 to form heteromeric channels with ORAI1 and to attenuate CRAC channel function...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28243166/orai1-and-orai3-in-combination-with-stim1-mediate-the-majority-of-store-operated-calcium-entry-in-astrocytes
#12
Jea Kwon, Heeyoung An, Moonsun Sa, Joungha Won, Jeong Im Shin, C Justin Lee
Astrocytes are non-excitable cells in the brain and their activity largely depends on the intracellular calcium (Ca(2+)) level. Therefore, maintaining the intracellular Ca(2+) homeostasis is critical for proper functioning of astrocytes. One of the key regulatory mechanisms of Ca(2+) homeostasis in astrocytes is the store-operated Ca(2+) entry (SOCE). This process is mediated by a combination of the Ca(2+)-store-depletion-sensor, Stim, and the store-operated Ca(2+)-channels, Orai and TrpC families. Despite the existence of all those families in astrocytes, previous studies have provided conflicting results on the molecular identification of astrocytic SOCE...
February 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#13
Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M Camp, Haiyang Tang, Shui Q Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F Machado
BACKGROUND: Pulmonary arterial hypertension is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT) is a cytozyme that regulates intracellular nicotinamide adenine dinucleotide levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation, and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling and that inhibition of NAMPT could attenuate pulmonary hypertension...
April 18, 2017: Circulation
https://www.readbyqxmd.com/read/28179072/orai3-channel-is-the-2-apb-induced-endoplasmic-reticulum-calcium-leak
#14
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 Ca2+ leak using synthetic Ca2+ indicators that report changes in both the cytoplasmic ([Ca2+ ]i ) and the luminal ER ([Ca2+ ]ER ) Ca2+ concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca2+ 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 [Ca2+ ]ER but did not decrease the ER Ca2+ leak after thapsigargin (TG)...
July 2017: Cell Calcium
https://www.readbyqxmd.com/read/28018223/pharmacological-characterization-of-the-native-store-operated-calcium-channels-of-cortical-neurons-from-embryonic-mouse-brain
#15
Sylvain Chauvet, Louis Jarvis, Mireille Chevallet, Niroj Shrestha, Klaus Groschner, Alexandre Bouron
In the murine brain, the first post-mitotic cortical neurons formed during embryogenesis express store-operated channels (SOCs) sensitive to Pyr3, initially proposed as a blocker of the transient receptor potential channel of C type 3 (TRPC3 channel). However, Pyr3 does not discriminate between Orai and TRPC3 channels, questioning the contribution of TRPC3 in SOCs. This study was undertaken to clarify the molecular identity and the pharmacological profile of native SOCs from E13 cortical neurons. The mRNA expression of STIM1-2 and Orai1-3 was assessed by quantitative reverse transcription polymerase chain reaction...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27881772/store-operated-calcium-channel-complex-in-postsynaptic-spines-a-new-therapeutic-target-for-alzheimer-s-disease-treatment
#16
Hua Zhang, Suya Sun, Lili Wu, Ekaterina Pchitskaya, Olga Zakharova, Klementina Fon Tacer, Ilya Bezprozvanny
Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca2+ influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca2+ channel complex in hippocampal mushroom spines...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27865925/orai1-and-orai2-mediate-store-operated-calcium-entry-that-regulates-hl60-cell-migration-and-fak-phosphorylation
#17
R Diez-Bello, I Jardin, G M Salido, J A Rosado
Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27617218/identification-of-trpcs-genetic-variants-that-modify-risk-for-lung-cancer-based-on-the-pathway-and-two-stage-study
#18
Zili Zhang, Jian Wang, Jianxing He, Xiansheng Zeng, Xindong Chen, Mingmei Xiong, Qipeng Zhou, Meihua Guo, Defu Li, Wenju Lu
OBJECTIVE: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca(2 +) concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. METHODS: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform...
September 2016: Meta Gene
https://www.readbyqxmd.com/read/27235552/hypoxic-stress-up-regulates-kir2-1-expression-and-facilitates-cell-proliferation-in-brain-capillary-endothelial-cells
#19
Hideto Yamamura, Yoshiaki Suzuki, Hisao Yamamura, Kiyofumi Asai, Yuji Imaizumi
The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4-5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba(2+)-sensitive inward rectifier K(+) current in t-BBEC117 cells after hypoxic culture...
August 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27041216/redox-modulation-of-stim-orai-signaling
#20
REVIEW
Rajesh Bhardwaj, Matthias A Hediger, Nicolas Demaurex
STIM1 and ORAI1 constitute the core machinery of the ubiquitous store-operated calcium entry pathway and loss of function in these proteins is associated with severe immune and muscular disorders. Other isoforms-STIM1L, STIM2, ORAI2 and ORAI3 exhibit varied expression levels in different cell types along with several other interaction partners and thereby play different roles to facilitate, regulate and fine-tune the calcium entry. STIM proteins convey the Ca(2+) store-depletion message to the PM and thereby participate in refilling of the ER by physically interacting with the Ca(2+)-selective ORAI channels at the PM...
August 2016: Cell Calcium
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