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https://www.readbyqxmd.com/read/29340082/reciprocal-sensitivity-of-diffuse-large-b-cell-lymphoma-cells-to-bcl-2-inhibitors-bird-2-versus-venetoclax
#1
Tamara Vervloessem, Haidar Akl, Thomas Tousseyn, Humbert De Smedt, Jan B Parys, Geert Bultynck
Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some cancers with elevated Bcl-2 display poor responses towards BH3 mimetics, suggesting an additional function for anti-apoptotic Bcl-2 in these cancers. Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5-trisphosphate receptor (IP3R)...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29330143/breast-cancer-targeting-through-inhibition-of-the-endoplasmic-reticulum-based-apoptosis-regulator-nrh-bcl2l10
#2
Adrien Nougarede, Nikolay Popgeorgiev, Loay Kassem, Soleilmane Omarjee, Stephane Borel, Ivan Mikaelian, Jonathan Lopez, Rudy Gadet, Olivier Marcillat, Isabelle Treilleux, Bruno O Villoutreix, Ruth Rimokh, Germain Gillet
Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in >45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum (ER)...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29323715/alleviation-of-palmitic-acid-induced-endoplasmic-reticulum-stress-by-augmenter-of-liver-regeneration-through-ip3r-controlled-ca2-release
#3
Wei-Chun Xiao, Zhang Jing, Si-Li Chen, Yi-Jun Shi, Fan Xiao, Wei An
The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non-alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR protection and the suppression of ER stress remains unclear. In this study, we investigated whether the protection against liver steatosis afforded by ALR is related to its inhibition of calcium overflow from the ER to the mitochondria...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29306025/silver-nanoparticles-induce-sh-sy5y-cell-apoptosis-via-endoplasmic-reticulum-and-mitochondrial-pathways-that-lengthen-endoplasmic-reticulum-mitochondria-contact-sites-and-alter-inositol-3-phosphate-receptor-function
#4
Lin Li, Jiahui Cui, Zi Liu, Xuejiao Zhou, Zengqiang Li, Yang Yu, Yuanyuan Jia, Daiying Zuo, Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response...
January 3, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29287955/remodeling-of-ca2-signaling-in-cancer-regulation-of-inositol-1-4-5-trisphosphate-receptors-through-oncogenes-and-tumor-suppressors
#5
REVIEW
Hideaki Ando, Katsuhiro Kawaai, Benjamin Bonneau, Katsuhiko Mikoshiba
The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that regulates diverse physiological and pathological processes, including cancer. Increasing evidence indicates that oncogenes and tumor suppressors regulate the Ca2+ transport systems. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-activated Ca2+ release channels located on the endoplasmic reticulum (ER). They play pivotal roles in the regulation of cell death and survival by controlling Ca2+ transfer from the ER to mitochondria through mitochondria-associated ER membranes (MAMs)...
December 20, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29284209/calcium-sensing-receptor-mediated-l-tryptophan-induced-secretion-of-cholecystokinin-and-glucose-dependent-insulinotropic-peptide-in-swine-duodenum
#6
Xiuying Zhao, Yihan Xian, Chao Wang, Liren Ding, Xianglong Meng, Weiyun Zhu, Suqin Hang
This study aimed to understand the effect of Tryptophan (Trp) on gut hormones secretion as well as the roles of the CaSR and its downstream signaling pathway in gut hormones secretion using swine duodenal perfusion in vitro. Swine duodenum was perfused with Krebs-Henseleit buffers (KHB) as a basal solution. Various concentrations (0, 10 mM and 20 mM) of Trp were applied to investigate the effect of Trp on gut hormones secretion. A CaSR antagonist was used to detect the involvement of CaSR and its signal molecules...
December 28, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29241198/fam3a-protects-against-glutamate-induced-toxicity-by-preserving-calcium-homeostasis-in-differentiated-pc12-cells
#7
Qing Song, Wen-Li Gou, Yu-Liang Zou
BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29207009/tat%C3%A2-fused-ip3r%C3%A2-derived-peptide-enhances-cisplatin-sensitivity-of-ovarian-cancer-cells-by-increasing-er-ca2-release
#8
Qi Xie, Ye Xu, Weinan Gao, Yong Zhang, Jing Su, Yanan Liu, Yuting Guo, Minghan Dou, Kebang Hu, Liankun Sun
Ovarian cancer is the most common gynecological malignancy. At present, cisplatin is used to treat ovarian cancer; however, the development of cisplatin resistance during therapy is a common obstacle to achieving favorable outcomes. Recently, the B‑cell lymphoma 2 (Bcl‑2) BH4 domain has been reported to mediate the prosurvival activity of Bcl‑2 in cancer; however, the involvement of the BH4 domain of Bcl‑2 in the cisplatin resistance of ovarian carcinoma cells is not entirely clear. In this study, we observed the cytoplasmic and mitochondrial levels of Ca2+ by confocal laser microscopy...
November 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29176553/notoginsenoside-r1-alleviates-oxygen-glucose-deprivation-reoxygenation-injury-by-suppressing-endoplasmic-reticulum-calcium-release-via-plc
#9
Yan Wang, Liu Tu, Yingbo Li, Di Chen, Zhao Liu, Xuelian Hu, Shali Wang
As documented in our previous study, notoginsenoside R1 (NGR1) can inhibit neuron apoptosis and the expression of endoplasmic reticulum (ER) stress-associated pro-apoptotic proteins in hypoxic-ischemic encephalopathy. Recent evidence indicates that the Phospholipase C (PLC)/inositol 1,4,5-trisphosphate receptor (IP3R) is important for the regulation of Ca2+ release in the ER. Ca2+ imbalance can stimulate ER stress, CAMKII, and cell apoptosis. The purpose of this study was to further investigate the neuroprotective effect of NGR1 and elucidate how NGR1 regulates ER stress and cell apoptosis in the oxygen-glucose deprivation/reoxygenation (OGD/R) model...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157865/peptide-yy-3-36-modulates-intracellular-calcium-through-activation-of-the-phosphatidylinositol-pathway-in-hippocampal-neurons
#10
Michelle Flores Domingues, Dênis Reis de Assis, Angela Regina Piovesan, Cháriston André Dal Belo, Jaderson Costa da Costa
Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca(2+) concentrations ([Ca(2+)]i) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures...
November 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29138405/ca-2-signals-initiate-at-immobile-ip3-receptors-adjacent-to-er-plasma-membrane-junctions
#11
Nagendra Babu Thillaiappan, Alap P Chavda, Stephen C Tovey, David L Prole, Colin W Taylor
IP3 receptors (IP3Rs) release Ca(2+) from the ER when they bind IP3 and Ca(2+). The spatial organization of IP3Rs determines both the propagation of Ca(2+) signals between IP3Rs and the selective regulation of cellular responses. Here we use gene editing to fluorescently tag endogenous IP3Rs, and super-resolution microscopy to determine the geography of IP3Rs and Ca(2+) signals within living cells. We show that native IP3Rs cluster within ER membranes. Most IP3R clusters are mobile, moved by diffusion and microtubule motors...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129205/the-steroid-hormone-20-hydroxyecdysone-upregulates-calcium-release-activated-calcium-channel-modulator-1-expression-to-induce-apoptosis-in-the-midgut-of-helicoverpa-armigera
#12
Yong-Bo Li, Xu-Yang Pei, Di Wang, Cai-Hua Chen, Mei-Juan Cai, Jin-Xing Wang, Xiao-Fan Zhao
Animal steroid hormones stimulate extracellular Ca(2+) influx into cells; however, the mechanism remains unclear. In this study, we determined that the Ca(2+) influx induced by steroid hormone 20-hydroxyecdysone (20E) is mediated by the calcium release-activated calcium channel modulator 1 (CRACM1/Orai1). The Orai1 mRNA is highly expressed during midgut programmed cell death in the lepidopteran insect Helicoverpa armigera. 20E upregulated the expression of Orai1 in H. armigera larvae and in an epidermal cell line (HaEpi)...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29127580/sigma-1-receptor-agonists-induce-oxidative-stress-in-mitochondria-and-enhance-complex-i-activity-in-physiological-condition-but-protect-against-pathological-oxidative-stress
#13
Nino Goguadze, Elene Zhuravliova, Didier Morin, Davit Mikeladze, Tangui Maurice
The sigma1 receptor (σ1R) is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it modulates Ca(2+) exchange between the ER and mitochondria by interacting with inositol-1,4,5 trisphosphate receptors (IP3Rs). The σ1R is highly expressed in the central nervous system and its activation stimulates neuromodulation and neuroprotection, for instance in Alzheimer's disease (AD) models in vitro and in vivo. σ1R effects on mitochondria pathophysiology and the downstream signaling are still not fully understood...
November 10, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29107242/silence-of-inositol-1-4-5-trisphosphate-receptor-expression-decreases-cyantraniliprole-susceptibility-in-bemisia-tabaci
#14
Lei Guo, Pei Liang, Kuan Fang, Dong Chu
Cyantraniliprole is the second active ingredient of anthranilic diamide insecticide, and the first to control a cross-spectrum of chewing and sucking pests such as sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). The inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) are two families of Ca(2+) release channels to raise the cytoplasmic free calcium concentration when it is activated by various extracellular stimuli. Previous study proved the over-expression of ryanodine receptor (RyR) was associated with the resistance to diamide insecticides, while the roles of IP3R in diamide resistance remain unknown...
October 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29074990/organelle-membrane-derived-patches-reshaping-classical-methods-for-new-targets
#15
George Shapovalov, Abigaël Ritaine, Gabriel Bidaux, Christian Slomianny, Anne-Sophie Borowiec, Dmitri Gordienko, Geert Bultynck, Roman Skryma, Natalia Prevarskaya
Intracellular ion channels are involved in multiple signaling processes, including such crucial ones as regulation of cellular motility and fate. With 95% of the cellular membrane belonging to intracellular organelles, it is hard to overestimate the importance of intracellular ion channels. Multiple studies have been performed on these channels over the years, however, a unified approach allowing not only to characterize their activity but also to study their regulation by partner proteins, analogous to the patch clamp "golden standard", is lacking...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29069790/downregulation-of-type-3-inositol-1-4-5-trisphosphate-receptor-decreases-breast-cancer-cell-migration-through-an-oscillatory-ca-2-signal
#16
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 (IP3Rs) remains enigmatic. If the three IP3Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP3R type 3 (IP3R3) 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
https://www.readbyqxmd.com/read/29066806/phosphoinositide-specific-phospholipase-c%C3%AE-1-inhibition-induces-autophagy-in-human-colon-cancer-and-hepatocellular-carcinoma-cells
#17
Lianzhi Dai, Xiaolei Chen, Xiaohong Lu, Fen Wang, Yanyan Zhan, Gang Song, Tianhui Hu, Chun Xia, Bing Zhang
Phosphoinositide-specific phospholipase C (PLC) γ1 has been reported to be involved in cancer cell proliferation and metastasis. However, whether PLCγ1 modulates autophagy and the underlying mechanism remains unclear. Here, we investigated the relationship between PLCγ1 and autophagy in the human colon cancer cell line HCT116 and hepatocellular carcinoma cell line HepG2. The results indicated that PLCγ1 inhibition via lentivirus-mediated transduction with shRNA/PLCγ1 or transient transfection with pRK5-PLCγ1 (Y783A) vector increased LC3B-II levels and the number of autophagic vacuoles and decreased p62 levels...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29060454/a-computational-model-of-intracellular-calcium-oscillations-in-urinary-bladder-smooth-muscle-cells
#18
Suranjana Gupta, Avni Majawadia, Rohit Manchanda
This paper presents a computational model for calcium (Ca(2+)) oscillations in detrusor smooth muscle (DSM) cells. The proposed model simulates the temporal profile of oscillations by incorporating various cellular and subcellular components. The cellular components include calcium influx via membrane and the plasma membrane calcium ATPase (PMCA) pump. The subcellular components include ryanodine receptors (RyRs), inositol 1, 4, 5 trisphosphate receptors (IP3Rs) and the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29054453/disruption-of-dopamine-d1-d2-receptor-complex-is-involved-in-the-function-of-haloperidol-in-cardiac-h9c2-cells
#19
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 (IP3R1). 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 IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats...
October 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29042597/herpud1-negatively-regulates-pathological-cardiac-hypertrophy-by-inducing-ip3-receptor-degradation
#20
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
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