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Lauren N Miterko, Joshua J White, Tao Lin, Amanda M Brown, Kevin J O'Donovan, Roy V Sillitoe
BACKGROUND: Purkinje cells play a central role in establishing the cerebellar circuit. Accordingly, disrupting Purkinje cell development impairs cerebellar morphogenesis and motor function. In the Car8wdl mouse model of hereditary ataxia, severe motor deficits arise despite the cerebellum overcoming initial defects in size and morphology. METHODS: To resolve how this compensation occurs, we asked how the loss of carbonic anhydrase 8 (CAR8), a regulator of IP3R1 Ca2+ signaling in Purkinje cells, alters cerebellar development in Car8wdl mice...
March 12, 2019: Neural Development
Monika Fluks, Katarzyna Szczepanska, Takao Ishikawa, Anna Maria Ajduk
In fully grown ovarian follicles both transcriptionally active (NSN) and inactive (SN) oocytes are present. NSN oocytes have been shown to display lower developmental potential. It is possible that oocytes that have not completed transcription before meiosis resumption accumulate less RNA and proteins required for their further development, including those responsible for regulation of Ca2+ homeostasis. Oscillations of the cytoplasmic concentration of free Ca2+ ions ([Ca2+]i) are triggered in oocytes by a fertilizing spermatozoon and are crucial for inducing and regulating further embryonic development...
February 1, 2019: Reproduction: the Official Journal of the Society for the Study of Fertility
Zaoni Li, Zhongxi Liu, V V Sathibabu Uddandrao, Ponmurugan Ponnusamy, Santhanaraj Balakrishnan, P Brahmanaidu, S Vadivukkarasi, Saravanan Ganapathy
In this study, we aimed at assessing the therapeutical potential of 6-gingerol ([5S]-5-hydroxy-1-[4-hydroxy- 3-methoxyphenyl]-3-decanone) against ovalbumin-sensitized asthma in rats. The rats were treated intraperitoneally with 6-gingerol (75 mg/kg body weight) for 30 days and a theophylline (200 mg/kg body weight)-treated group as a control. Changes in the levels of T-cell-linked cytokines (interleukin-4 [IL-4], IL-5, IL-13, and interferon-gamma [IFN-?]), total immunoglobulin E (IgE), gene expressions of bitter taste-sensing type 2-receptor 10 (T2R10), inositol 1,4,5-triphosphate receptor 1 (IP3R1), Orai1 and protein expressions of nuclear factor of activated T cells 1 (NFAT1), c-Myc and histopathological changes were observed in rats...
2019: Journal of Environmental Pathology, Toxicology and Oncology
Christos Michael Suriano
The Inositol 1,4,5-trisphosphate receptor type 1 protein (Ip3r1) performs an essential role for the induction of cerebellar long-term depression. Here, I describe the use of RT-PCR, qPCR, western blotting and immunohistochemistry to assay Ip3r1 gene expression and localize Ip3r1 protein in the hindbrain of the elasmobranch fish, Leucoraja erinacea . Elasmobranchs are representatives of the most basal, yet extant lineage of gnathostomes, or jawed vertebrates. The cerebellum is a synapomorphy for gnathostomes and thus elasmobranch cerebellar physiology may serve as a proxy for the ancestral state of other jawed vertebrates...
January 2019: Heliyon
Minerva Ferrer-Buitrago, Davina Bonte, Lien Dhaenens, Sanne Vermorgen, Yuechao Lu, Petra De Sutter, Björn Heindryckx
RESEARCH QUESTION: Can oocyte-related activation deficiencies be evaluated in oocytes that failed to fertilize after intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA)? DESIGN: Evaluation of the spindle-chromosome complexes and intracellular distribution of inositol trisphosphate type 1 receptors (IP3R1) in in-vitro matured (IVM) and failed-to-fertilize oocytes from patients undergoing AOA. Assessment of the oocyte-related Ca2+ releasing capacity in response to Ca2+ ionophores and sperm microinjection in oocytes that failed to fertilize after ICSI or ICSI-AOA...
December 23, 2018: Reproductive Biomedicine Online
Themis Thoudam, Chae-Myeong Ha, Jaechan Leem, Dipanjan Chanda, Jong-Seok Park, Hyo-Jeong Kim, Jae-Han Jeon, Yeon-Kyung Choi, Suthat Liangpunsakul, Yang Hoon Huh, Tae-Hwan Kwon, Keun-Gyu Park, Robert A Harris, Kyu-Sang Park, Hyun-Woo Rhee, In-Kyu Lee
Mitochondria-associated ER membrane (MAM) is a structural link between mitochondria and endoplasmic reticulum (ER). MAM regulates Ca2+ transport from the ER to mitochondria via an IP3R1-GRP75-VDAC1 complex-dependent mechanism. Excessive MAM formation may cause mitochondrial Ca2+ overload and mitochondrial dysfunction. However, the exact implication of MAM formation in metabolic syndromes remains debatable. Here, we demonstrate that pyruvate dehydrogenase kinase 4 (PDK4) interacts with and stabilizes IP3R1-GRP75-VDAC1 complex at the MAM interface...
December 6, 2018: Diabetes
Sevtap Han, Nur Banu Bal, Gökhan Sadi, Suzan Emel Usanmaz, Mecit Orhan Uludag, Emine Demirel-Yilmaz
AIMS: Liver X receptors (LXRs) play an important role in the regulation of cholesterol, fatty acid and glucose metabolisms together with inflammatory processes. In the present study, the effects of LXR agonist GW3965 on vascular reactivity and expression of functional proteins in DOCA-Salt induced hypertension were examined. MAIN METHODS: Hypertension was induced through unilateral nephrectomy and deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) for 6 weeks in male Wistar albino rats (8 weeks old)...
October 23, 2018: Life Sciences
Chenguang Xu, Yan Fang, Zhiyong Yang, Yukai Jing, Yonghui Zhang, Chaohong Liu, Wanli Liu
Tonic or chronic active B-cell receptor (BCR) signaling is essential for the survival of normal or some malignant B cells, respectively. However, the molecular mechanism regulating the strength of these two types of BCR signaling remains unknown. Here, using high-speed high-resolution single-molecule tracking in live cells, we identified that PKCβ, STIM1, and IP3R1/2/3 molecules affected the lateral Brownian mobile behavior of BCRs on the plasma membrane of quiescent B cells, which was correlated to the strength of BCR signaling...
September 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xiaolong Wang, Hao Yu, Jiabin You, Changliang Wang, Chunmei Feng, Zhaodi Liu, Ya Li, Rucheng Wei, Siqi Xu, Rui Zhao, Xu Wu, Guohua Zhang
Chronic ethanol intake can induce neuronal apoptosis, leading to dementia. We investigated the protective effects of memantine on spatial memory impairment induced by chronic ethanol exposure in mice. Male C57BL/6 mice were administered 10% (m/V) or 20% (m/V) ethanol as the only choice of drinking water. Mice were treated for 60 d, 90 d, or 180 d. Mice were treated with memantine for the same duration (daily 10 mg/kg oral). The Morris water maze and radial arm maze test were used to measure spatial memory...
August 1, 2018: Toxicology
Vishal R Yadav, Tengyao Song, Lin Mei, Leroy Joseph, Yun-Min Zheng, Yong-Xiao Wang
Hypoxia-induced pulmonary vasoconstriction (HPV) is attributed to an increase in intracellular Ca2+ concentration ([Ca2+ ]i ) in pulmonary artery smooth muscle cells (PASMCs). We have reported that phospholipase C-γ1 (PLCγ1) plays a significant role in the hypoxia-induced increase in [Ca2+ ]i in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca2+ and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in pulmonary arteries, but not in mesenteric arteries...
May 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Dong-Lei Wang, Wen-Ying Dai, Wen Wang, Ying Wen, Ying Zhou, Yi-Tong Zhao, Jian Wu, Pei Liu
We have reported that tumor necrosis factor-α (TNF-α) is critical for reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic failure (FHF). The present study aims to evaluate the underlying mechanisms of decreased GFR during acute hepatic failure. Rats with FHF induced by d-galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with recombinant lentivirus harboring short hairpin RNA against the protein kinase C-α ( PKC-α) gene (Lenti-shRNA-PKC-α). GFR, serum levels of aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF-α, and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate receptor (IP3 R1) expression in renal tissue were assessed...
May 1, 2018: American Journal of Physiology. Renal Physiology
Sung Jin Park, Su Been Lee, Yeongjun Suh, Su-Jeong Kim, Namgyu Lee, Ji-Ho Hong, Cana Park, Youngsik Woo, Koko Ishizuka, Joung-Hun Kim, Per-Olof Berggren, Akira Sawa, Sang Ki Park
A wide range of Ca2+ -mediated functions are enabled by the dynamic properties of Ca2+ , all of which are dependent on the endoplasmic reticulum (ER) and mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM). At the MAM, DISC1 interacts with IP3 R1 and downregulates its ligand binding, modulating ER-mitochondria Ca2+ transfer through the MAM...
December 5, 2017: Cell Reports
Cheng-Tsung Hsiao, Yo-Tsen Liu, Yi-Chu Liao, Ting-Yi Hsu, Yi-Chung Lee, Bing-Wen Soong
BACKGROUND: The inositol 1,4,5-triphosphate (IP3) receptor type 1 gene (ITPR1) encodes the IP3 receptor type 1 (IP3R1), which modulates intracellular calcium homeostasis and signaling. Mutations in ITPR1 have been implicated in inherited cerebellar ataxias. The aim of this study was to investigate the role of ITPR1 mutations, including both large segmental deletion and single nucleotide mutations, in a Han Chinese cohort with inherited cerebellar ataxias in Taiwan. METHODOLOGY AND PRINCIPAL FINDINGS: Ninety-three unrelated individuals with molecularly unassigned spinocerebellar ataxia selected from 585 pedigrees with autosomal dominant cerebellar ataxias, were recruited into the study with elaborate clinical evaluations...
2017: PloS One
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 (IP3 Rs) remains enigmatic. If the three IP3 Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP3 R type 3 (IP3 R3 ) 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
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 (IP3 R1). 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 IP3 R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats...
December 15, 2017: Life Sciences
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 Ca2+ 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 Ca2+ 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
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
Jie Tong, Ying Qi, Xiangmiao Wang, Liyin Yu, Chang Su, Wenjun Xie, Jianbao Zhang
The mechanism by which cell shape regulates the function of the cell is one of the most important biological issues, but it remains unclear. Here, we investigated the effect of the regulation of cell shape on proliferation by using a micropatterning approach to confine MC3T3-E1 cells into specific shapes. Our results show that the proliferation rate for rectangle-, triangle-, square- and circle-shaped osteoblasts increased sequentially and was related to the nuclear shape index (NSI) but not the cell shape index (CSI)...
December 2017: Biochimica et Biophysica Acta. Molecular Cell Research
Xue-Ming Zhao, Na Wang, Hai-Sheng Hao, Chong-Yang Li, Ya-Han Zhao, Chang-Liang Yan, Hao-Yu Wang, Wei-Hua Du, Dong Wang, Yan Liu, Yun-Wei Pang, Hua-Bin Zhu
Melatonin is a well-characterized antioxidant that has been successfully used to protect oocytes from reactive oxygen species during in vitro maturation (IVM), resulting in improved fertilization capacity and development ability. However, the mechanism via which melatonin improves oocyte fertilization capacity and development ability remains to be determined. Here, we studied the effects of melatonin on cytoplasmic maturation of bovine oocytes. In the present study, bovine oocytes were cultured in IVM medium supplemented with 0, 10-7 , 10-9 , and 10-11  mol/L melatonin, and the cytoplasmic maturation parameters of MII oocytes after IVM were investigated, including redistribution of organelles (mitochondria, cortical granules [CGs], and endoplasmic reticulum [ER]), intracellular glutathione (GSH) and ATP levels, expression of endogenous antioxidant genes (Cat, Sod1, and GPx), and fertilization-related events (IP3R1 distribution and expression of CD9 and Juno)...
January 2018: Journal of Pineal Research
Jana Kubickova, Lubomira Lencesova, Lucia Csaderova, Tibor Stracina, Sona Hudecova, Petr Babula, Eva Rozborilova, Marie Novakova, Olga Krizanova
Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IP3 Rs). Aim of this work was to investigate possible changes in IP3 Rs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.e., effect on cellular plasticity. Haloperidol treatment resulted in up-regulation of both type 1 IP3 Rs (IP3 R1s) and σ1Rs at mRNA and protein levels...
January 2018: Cellular and Molecular Neurobiology
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