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https://www.readbyqxmd.com/read/28419336/ip3r-mediated-ca2-signals-govern-hematopoietic-and-cardiac-divergence-of-flk1-cells-via-the-calcineurin-nfatc3-etv2-pathway
#1
Yi-Jie Wang, Jijun Huang, Wenqiang Liu, Xiaochen Kou, Huayuan Tang, Hong Wang, Xiujian Yu, Shaorong Gao, Kunfu Ouyang, Huang-Tian Yang
Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced Flk1+/PDGFRα- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes...
April 13, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28417016/hmgb1-release-by-h2o2-induced-hepatocytes-is-regulated-through-calcium-overload-and-58-f-interference
#2
Pei Zhao, Tingjie Ye, Xiaofeng Yan, Xudong Hu, Ping Liu, Xiaoling Wang
HMGB1 is passively released by injured or dying cells and aggravates inflammatory processes. The release of HMGB1 and calcium overload have each been reported to be important mediators of H2O2-induced injury. However, a potential connection between these two processes remains to be elucidated. In the present study, we employed H2O2-induced hepatocytes to investigate how calcium overload takes place during cellular injury and how the extracellular release of HMGB1 is regulated by this overload. In addition, we investigated the use of 58-F, a flavanone extracted from Ophiopogon japonicus, as a potential therapeutic drug...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28416699/ip3-mediated-gating-mechanism-of-the-ip3-receptor-revealed-by-mutagenesis-and-x-ray-crystallography
#3
Kozo Hamada, Hideyuki Miyatake, Akiko Terauchi, Katsuhiko Mikoshiba
The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion channel that releases calcium ions (Ca(2+)) from the endoplasmic reticulum. The IP3-binding sites in the large cytosolic domain are distant from the Ca(2+) conducting pore, and the allosteric mechanism of how IP3 opens the Ca(2+) channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP3R in the absence and presence of IP3 Analyses of two distinct space group crystals uncovered an IP3-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28413728/mechanism-of-endothelial-nitric-oxide-synthase-phosphorylation-and-activation-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#4
Beilei Wang, Dan Liu, Chao Wang, Qianqian Wang, Hui Zhang, Guoyan Liu, Xia Tao, Liming Zhang
Our previous study demonstrated that tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) could cause a weak relaxation response mediated by nitric oxide (NO) using isolated aorta rings. However, the intracellular mechanisms of TE-induced vasodilation remain unclear. Thus, this study was conducted to examine the role of TE on Akt/eNOS/NO and Ca(2+) signaling pathways in human umbilical vein endothelial cells (HUVECs). Our results showed that TE induced dose- and time-dependent increases of eNOS activity and NO production...
2017: PeerJ
https://www.readbyqxmd.com/read/28390800/ca-2-release-via-two-pore-channel-type-2-tpc2-is-required-for-slow-muscle-cell-myofibrillogenesis-and-myotomal-patterning-in-intact-zebrafish-embryos
#5
Jeffrey J Kelu, Sarah E Webb, John Parrington, Antony Galione, Andrew L Miller
We recently demonstrated a critical role for two-pore channel type 2 (TPC2)-mediated Ca(2+) release during the differentiation of slow (skeletal) muscle cells (SMC) in intact zebrafish embryos, via the introduction of a translational-blocking morpholino antisense oligonucleotide (MO). Here, we extend our study and demonstrate that knockdown of TPC2 with a non-overlapping splice-blocking MO, knockout of TPC2 (via the generation of a tpcn2(dhkz1a) mutant line of zebrafish using CRISPR/Cas9 gene-editing), or the pharmacological inhibition of TPC2 action with bafilomycin A1 or trans-ned-19, also lead to a significant attenuation of SMC differentiation, characterized by a disruption of SMC myofibrillogenesis and gross morphological changes in the trunk musculature...
April 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28381466/intracellular-angiotensin-ii-interacts-with-nuclear-angiotensin-receptors-in-cardiac-fibroblasts-and-regulates-rna-synthesis-cell-proliferation-and-collagen-secretion
#6
Artavazd Tadevosyan, Jiening Xiao, Sirirat Surinkaew, Patrice Naud, Clémence Merlen, Masahide Harada, Xiaoyan Qi, David Chatenet, Alain Fournier, Bruce G Allen, Stanley Nattel
BACKGROUND: Cardiac fibroblasts play important functional and pathophysiological roles. Intracellular ("intracrine") angiotensin-II (Ang-II) signaling regulates intercellular communication, excitability, and gene expression in cardiomyocytes; however, the existence and role of intracrine Ang-II signaling in cardiac fibroblasts is unstudied. Here, we evaluated the localization of Ang-II receptors on atrial fibroblast nuclei and associated intracrine effects of potential functional significance...
April 5, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28348216/splicing-variation-of-long-irbit-determines-the-target-selectivity-of-irbit-family-proteins
#7
Katsuhiro Kawaai, Hideaki Ando, Nobuhiko Satoh, Hideomi Yamada, Naoko Ogawa, Matsumi Hirose, Akihiro Mizutani, Benjamin Bonneau, George Seki, Katsuhiko Mikoshiba
IRBIT [inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with inositol 1,4,5-trisphosphate (IP3)] is a multifunctional protein that regulates several target molecules such as ion channels, transporters, polyadenylation complex, and kinases. Through its interaction with multiple targets, IRBIT contributes to calcium signaling, electrolyte transport, mRNA processing, cell cycle, and neuronal function. However, the regulatory mechanism of IRBIT binding to particular targets is poorly understood...
March 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28337264/ip3r-and-ryr-calcium-channels-are-involved-in-neonatal-rat-cardiac-myocyte-hypertrophy-induced-by-tumor-necrosis-factor-%C3%AE
#8
Gui-Jun Wang, Lian-Yi Guo, Hong-Xin Wang, Yu-Sheng Yao
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca(2+)]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336440/astroglial-ca-2-signaling-is-generated-by-the-coordination-of-ip3r-and-store-operated-ca-2-channels
#9
Shigeo Sakuragi, Fumihiro Niwa, Yoichi Oda, Hiroko Bannai, Katsuhiko Mikoshiba
Astrocytes play key roles in the central nervous system and regulate local blood flow and synaptic transmission via intracellular calcium (Ca(2+)) signaling. Astrocytic Ca(2+) signals are generated by multiple pathways: Ca(2+) release from the endoplasmic reticulum (ER) via the inositol 1, 4, 5-trisphosphate receptor (IP3R) and Ca(2+) influx through various Ca(2+) channels on the plasma membrane. However, the Ca(2+) channels involved in astrocytic Ca(2+) homeostasis or signaling have not been fully characterized...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28333380/smooth-muscle-ion-channels-and-regulation-of-vascular-tone-in-resistance-arteries-and-arterioles
#10
Nathan R Tykocki, Erika M Boerman, William F Jackson
Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body's tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28322744/basal-ryanodine-receptor-activity-suppresses-autophagic-flux
#11
Tim Vervliet, Isabel Pintelon, Kirsten Welkenhuyzen, Martin D Bootman, Hiroko Bannai, Katsuhiko Mikoshiba, Wim Martinet, Nael Nadif Kasri, Jan B Parys, Geert Bultynck
The inositol 1,4,5-trisphosphate receptors (IP3Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology...
March 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28316566/blockade-of-ryrs-in-the-er-attenuates-6-ohda-induced-calcium-overload-cellular-hypo-excitability-and-apoptosis-in-dopaminergic-neurons
#12
Lu Huang, Ying Xue, DaYun Feng, RuiXin Yang, Tiejian Nie, Gang Zhu, Kai Tao, GuoDong Gao, Qian Yang
Calcium (Ca(2+)) dyshomeostasis induced by endoplasmic reticulum (ER) stress is an important molecular mechanism of selective dopaminergic (DA) neuron loss in Parkinson's disease (PD). Inositol 1,4,5-triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), which are located on the ER surface, are the main endogenous Ca(2+) release channels and play crucial roles in regulating Ca(2+) homeostasis. However, the roles of these endogenous Ca(2+) release channels in PD and their effects on the function and survival of DA neurons remain unknown...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28303572/intracellular-calcium-release-channels-an-update
#13
Gaetano Santulli, Ryutaro Nakashima, Qi Yuan, Andrew R Marks
Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are calcium (Ca(2+) ) release channels on the endo/sarcoplasmic reticulum (ER/SR). Here we summarize the latest advances in the field, describing the recently discovered mechanistic roles of intracellular Ca(2+) release channels in the regulation of mitochondrial fitness and endothelial function, providing novel therapeutic options for the treatment of heart failure, hypertension, and diabetes mellitus. This article is protected by copyright...
March 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28289132/ip3r-mediated-ca-2-release-regulates-protein-metabolism-in-drosophila-neuroendocrine-cells-implications-for-development-under-nutrient-stress
#14
Megha, Gaiti Hasan
Successful completion of animal development is fundamentally reliant on nutritional cues. Adaptations for surviving nutritional loss are coordinated in part by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells critically modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation, if either insulin signaling or IP3/Ca(2+) signaling, were down-regulated in NE cells. Moreover, an IP3R (Inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by over-expression of either InR (insulin receptor) or IP3R in NE cells of the mutant, suggesting that the two signaling pathways may be functionally compensatory...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#15
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28254579/resveratrol-induced-autophagy-is-dependent-on-ip3rs-and-on-cytosolic-ca-2
#16
Tomas Luyten, Kirsten Welkenhuyzen, Gemma Roest, Elzbieta Kania, Liwei Wang, Mart Bittremieux, David I Yule, Jan B Parys, Geert Bultynck
Previous work revealed that intracellular Ca(2+) signals and the inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) are essential to increase autophagic flux in response to mTOR inhibition, induced by either nutrient starvation or rapamycin treatment. Here, we investigated whether autophagy induced by resveratrol, a polyphenolic phytochemical reported to trigger autophagy in a non-canonical way, also requires IP3Rs and Ca(2+) signaling. Resveratrol augmented autophagic flux in a time-dependent manner in HeLa cells...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28247051/oocyte-activation-and-fertilisation-crucial-contributors-from-the-sperm-and-oocyte
#17
Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Kevin Coward
This chapter intends to summarise the importance of sperm- and oocyte-derived factors in the processes of sperm-oocyte binding and oocyte activation. First, we describe the initial interaction between sperm and the zona pellucida, with particular regard to acrosome exocytosis. We then describe how sperm and oocyte membranes fuse, with special reference to the discovery of the sperm protein IZUMO1 and its interaction with the oocyte membrane receptor JUNO. We then focus specifically upon oocyte activation, the fundamental process by which the oocyte is alleviated from metaphase II arrest by a sperm-soluble factor...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28237722/dapper1-attenuates-hepatic-gluconeogenesis-and-lipogenesis-by-activating-pi3k-akt-signaling
#18
Jian-Ren Kuang, Zhi-Hui Zhang, Wei-Ling Leng, Xiao-Tian Lei, Zi-Wen Liang
Studies have shown that hepatic insulin resistance, a disorder of glucose and lipid metabolism, plays a vital role in type 2 diabetes (T2D). To clarify the function of Dapper1 in glucose and lipid metabolism in the liver, we investigated the relationships between Dapper1 and adenosine triphosphate (ATP)- and Ca(2+)-mediated activation of PI3K/Akt. We observed a reduction in hepatic Dapper1 in db/db (mice that are homozygous for a spontaneous diabetes mutation) and HFD-induced diabetic mice with T2D. Hepatic overexpression of Dapper1 improved hyperglycemia, insulin resistance, and fatty liver...
February 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28196740/dpb162-ae-an-inhibitor-of-store-operated-ca-2-entry-can-deplete-the-endoplasmic-reticulum-ca-2-store
#19
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
#20
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
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