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https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#1
Manami Kaneko, Hisato Yamamoto, Hiroki Sakai, Yusuke Kamada, Toshiki Tanaka, Shuji Fujiwara, Synsuke Yamamoto, Hiroki Takahagi, Hideyuki Igawa, Shizuo Kasai, Masakuni Noda, Makoto Inui, Tomoyuki Nishimoto
The cardiac sarco/endoplasmic reticulum Ca(2+)-dependent ATPase 2a (SERCA2a) plays a central role in Ca(2+) handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca(2+)-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28733226/allatoregulatory-like-systems-and-changes-in-cytosolic-ca-2-modulate-feeding-behaviour-in-hydra
#2
María Eugenia Alzugaray, Jorge Rafael Ronderos
Allatotropin (AT) and allatostatin-C (AST-C) are neuropeptides originally characterized by their ability to modulate the secretion of juvenile hormones in insects. Beyond the allatoregulatory function, these neuropeptides are pleiotropic acting as myoregulators not only in insects, but also in other groups of invertebrates. We have previously proposed the existence of AT and AST-C like systems in Hydra sp., a member of the phylum Cnidaria, which is a basal group of Metazoa, sharing a common ancestor with Bilateria...
July 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28721361/role-of-endoplasmic-reticulum-stress-in-learning-and-memory-impairment-and-alzheimer-s-disease-like-neuropathology-in-the-ps19-and-app-swe-mouse-models-of-tauopathy-and-amyloidosis
#3
Denise Isabelle Briggs, Erwin Defensor, Pooneh Memar Ardestani, Bitna Yi, Michelle Halpain, Guy Seabrook, Mehrdad Shamloo
Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28713161/functional-expression-of-the-ca-2-signaling-machinery-in-human-embryonic-stem-cells
#4
Ji-Jun Huang, Yi-Jie Wang, Min Zhang, Peng Zhang, He Liang, Hua-Jun Bai, Xiu-Jian Yu, Huang-Tian Yang
Emerging evidence suggests that Ca(2+) signals are important for the self-renewal and differentiation of human embryonic stem cells (hESCs). However, little is known about the physiological and pharmacological properties of the Ca(2+)-handling machinery in hESCs. In this study we used RT-PCR and Western blotting to analyze the expression profiles of genes encoding Ca(2+)-handling proteins; we also used confocal Ca(2+) imaging and pharmacological approaches to determine the contribution of the Ca(2+)-handling machinery to the regulation of Ca(2+) signaling in hESCs...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28711908/the-2-aminoethoxydiphenyl-borate-analog-dpb161-blocks-store-operated-ca2-entry-in-acutely-dissociated-rat-submandibular-cells
#5
Kunkun Xia, Zegang Ma, Jianxin Shen, Menghan Li, Baoke Hou, Ming Gao, Shuijun Zhang, Jie Wu
Cellular Ca2+ signals play a critical role in cell physiology and pathology. In most non-excitable cells, store-operated Ca2+ entry (SOCE) is an important mechanism by which intracellular Ca2+ signaling is regulated. However, few drugs can selectively modulate SOCE. 2-Aminoethoxydiphenyl borate (2APB) and its analogs (DPB162 and DPB163) have been reported to inhibit SOCE. Here, we examined the effects of another 2-APB analog, DPB161 on SOCE in acutely-isolated rat submandibular cells. Both patch-clamp recordings and Ca2+ imaging showed that upon removal of extracellular Ca2+ ([Ca2+]o=0), rat submandibular cells were unable to maintain ACh-induced Ca2+ oscillations, but restoration of [Ca2+]o to refill Ca2+ stores enable recovery of these Ca2+ oscillations...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707279/sarcolipin-expression-is-repressed-by-endoplasmic-reticulum-stress-in-c2c12-myotubes
#6
Nobuhiko Takahashi, Atsushi P Kimura, Sumiyoshi Naito, Mika Yoshida, Osamu Kumano, Takeshi Suzuki, Satoshi Itaya, Mitsuru Moriya, Masahiro Tsuji, Masahiro Ieko
Sarcolipin is a transmembrane protein expressed in the sarco/endoplasmic reticulum of skeletal and atrial muscles in large animals. Sarcolipin plays crucial roles in heat production through modifying the function of sarco/endoplasmic reticulum Ca(2+) ATPase, thereby being involved in thermogenesis and systemic metabolism. In skeletal muscle, endoplasmic reticulum (ER) stress has been implicated in several conditions, such as insulin resistance, muscle diseases, and hypo/hyper-contraction. Here, we investigated the effect of ER stress on sarcolipin expression in skeletal muscle cells, C2C12 myotubes...
July 13, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28703114/inhibition-of-perk-dependent-pro-adaptive-signaling-pathway-as-a-promising-approach-for-cancer-treatment
#7
Wioletta Rozpędek, Dariusz Pytel, Łukasz Dziki, Alicja Nowak, Adam Dziki, J Alan Diehl, Ireneusz Majsterek
Endoplasmic Reticulum (ER) is an organelle that is vital for cell growth and maintenance of homeostasis. Recent studies have reported that numerous human diseases, including cancer, are strictly connected to disruption of ER homeostasis. In order to counteract adverse intracellular conditions, cancer cells induce protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-dependent, pro-adaptive unfolded protein response (UPR) signaling branches. If ER stress is severe or prolonged, pro-adaptive signaling networks are insufficient, resulting in apoptotic cell death of cancer cells...
June 30, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/28699288/different-characteristics-of-cell-volume-and-intracellular-calcium-ion-concentration-dynamics-between-the-hippocampal-ca1-and-lateral-cerebral-cortex-of-male-mouse-brain-slices-during-exposure-to-hypotonic-stress
#8
Nanae Takahashi, Akibumi Omi, Hiroyuki Uchino, Yoshihisa Kudo
The mechanism of brain edema is complex and still remains unclear. Our aim was to investigate the regional differences of cell volume and intracellular Ca(2+) concentration ([Ca(2+) ]i ) dynamics during hypotonic stress in male mouse hemi-brain slices. Brain slices were loaded with the fluorescence Ca(2+) indicator fura-2, and cell volume and [Ca(2+) ]i in the lateral cerebral cortex (LCC) and hippocampal CA1 (CA1) region were measured simultaneously during exposure to hypotonic stress using Ca(2+) insensitive (F360) and Ca(2+) sensitive fluorescence (F380), respectively...
July 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28698383/pancreatic-%C3%AE-cell-protection-from-inflammatory-stress-by-the-endoplasmic-reticulum-proteins-thrombospondin-1-and-mesencephalic-astrocyte-derived-neutrotrophic-factor-manf
#9
Daniel A Cunha, Monia Cito, Fabio A Grieco, Cristina Cosentino, Tatiana Danilova, Laurence Ladriere, Maria Lindahl, Andrii Domanskyi, Marco Bugliani, Piero Marchetti, Decio L Eizirik, Miriam Cnop
Cytokine-induced endoplasmic reticulum (ER) stress is one of the molecular mechanisms underlying pancreatic β-cell demise in type 1 diabetes. Thrombospondin-1 (THBS1) was recently shown to promote β-cell survival during lipotoxic stress. Here we show that ER-localized THBS1 is cytoprotective to rat, mouse and human β-cells exposed to cytokines or thapsigargin-induced ER stress. THBS1 confers cytoprotection by maintaining expression of mesencephalic astrocyte-derived neutrotrophic factor (MANF) in β-cells, and thereby prevents the BH3-only protein BIM-dependent triggering of the mitochondrial pathway of apoptosis...
July 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28697919/fatty-acid-translocase-promoted-hepatitis-b-virus-replication-by-upregulating-the-levels-of-hepatic-cytosolic-calcium
#10
Jian Huang, Lei Zhao, Ping Yang, Zhen Chen, Xiong Z Ruan, Ailong Huang, Ni Tang, Yaxi Chen
Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS...
July 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28674530/endoplasmic-reticulum-stress-sensor-ire1%C3%AE-enhances-il-23-expression-by-human-dendritic-cells
#11
Saioa Márquez, José Javier Fernández, Eli Terán-Cabanillas, Carmen Herrero, Sara Alonso, Alicia Azogil, Olimpio Montero, Takao Iwawaki, Juan R Cubillos-Ruiz, Nieves Fernández, Mariano Sánchez Crespo
Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28667329/imipramine-blue-sensitively-and-selectively-targets-flt3-itd-positive-acute-myeloid-leukemia-cells
#12
Jonathan Metts, Heath L Bradley, Zhengqi Wang, Neil P Shah, Reuben Kapur, Jack L Arbiser, Kevin D Bunting
Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28652211/chop-negatively-regulates-polo-like-kinase-2-expression-via-recruiting-c-ebp%C3%AE-to-the-upstream-promoter-in-human-osteosarcoma-cell-line-during-er-stress
#13
Tao Shen, Yan Li, Zhiguang Chen, Shuang Liang, Zhouyang Guo, Ping Wang, Qijun Wu, Gen Ba, Qin Fu
Polo-like kinase 2 (Plk2) is a member of the serine/threonine protein kinase family involved in cell-cycle regulation and cellular response to stresses. However, the alteration of Plk2 in response to endoplasmic reticulum (ER) stress has not been well described. In the present study, we focused on the regulation of Plk2 regulation in response to ER stress. Plk2 expression was dramatically decreased under ER stress induced by brefeldin A (BFA), thapsigargin (TG), or tunicamycin (TM), and this down regulation of Plk2 expression was dependent on activating transcription factor 4 (ATF4) and C/EBP homology protein (CHOP)...
June 24, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28640982/mechanisms-of-sphingosine-1-phosphate-mediated-vasoconstriction-of-rat-afferent-arterioles
#14
Z Guan, F Wang, X Cui, E W Inscho
AIM: Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent vasoconstriction of the pre-glomerular microvasculature, but the underlying mechanisms remain incompletely defined. We postulated that S1P-mediated pre-glomerular microvascular vasoconstriction involves activation of voltage-dependent L-type calcium channels (L-VDCC) and the rho/rho kinase pathway. METHODS: Afferent arteriolar reactivity was assessed in vitro using the blood-perfused rat juxtamedullary nephron preparation, and diameter was measured during exposure to physiological and pharmacological agents...
June 22, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28638347/bile-acids-do-not-contribute-to-the-altered-calcium-homeostasis-of-platelets-from-rats-with-biliary-cirrhosis
#15
Paola Romecín, Esther G Navarro, M Clara Ortiz, David Iyú, Joaquín García-Estañ, Noemí M Atucha
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28637792/reactive-sulfur-species-inactivate-ca-2-calmodulin-dependent-protein-kinase-iv-via-s-polysulfidation-of-its-active-site-cysteine-residue
#16
Tsuyoshi Takata, Hideshi Ihara, Naoya Hatano, Yukihiro Tsuchiya, Takaaki Akaike, Yasuo Watanabe
Reactive sulfur species (RSS) modulate protein functions via S- polysulfidation of reactive Cys residues. Here, we report that Ca(2+)/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) was reversibly inactivated by RSS via polysulfidation of the active site Cys residue. CaMKIV is phosphorylated at Thr(196) by its upstream CaMK kinase (CaMKK), resulting in the induction of its full activity. In vitro incubation of CaMKIV with the exogenous RSS donors Na2Sn ( n = 2-4) resulted in dose-dependent inhibition of the CaMKK-induced phospho-Thr(196) and consequent inactivation of the enzyme activity...
June 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28637791/store-operated-calcium-entry-suppressed-tgf%C3%AE-1-smad3-signaling-pathway-in-glomerular-mesangial-cells
#17
Sarika Chaudhari, Weizu Li, Yanxia Wang, Hui Jiang, Yuhong Ma, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca2+ entry in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor beta 1 (TGFβ1) - Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGFβ1 (5 ng/ml for 15 hours) significantly increased Smad3 phosphorylation as evaluated by immunoblot...
June 21, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28634818/sg2na-is-a-regulator-of-endoplasmic-reticulum-er-homeostasis-as-its-depletion-leads-to-er-stress
#18
Buddhi Prakash Jain, Shweta Pandey, Nikhat Saleem, Goutam K Tanti, Shalini Mishra, Shyamal K Goswami
SG2NA belongs to a three-member striatin subfamily of WD40 repeat superfamily of proteins. It has multiple protein-protein interaction domains involved in assembling supramolecular signaling complexes. Earlier, we had demonstrated that there are at least five variants of SG2NA generated by alternative splicing, intron retention, and RNA editing. Such versatile and dynamic mode of regulation implicates it in tissue development. In order to shed light on its role in cell physiology, total proteome analysis was performed in NIH3T3 cells depleted of 78 kDa SG2NA, the only isoform expressing therein...
June 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28624282/effect-of-endoplasmic-reticulum-stress-on-metabolic-and-stress-signaling-and-kidney-specific-functions-in-madin-darby-bovine-kidney-cells
#19
E Chiappisi, R Ringseis, K Eder, D K Gessner
Recent studies demonstrated induction of endoplasmic reticulum (ER) stress in tissues of cows after parturition, but knowledge about the effect of ER stress on important cellular processes, such as critical signaling and metabolic pathways, in cattle is scarce. Thus, the present study aimed to investigate the effect of ER stress induction on nuclear factor-κB (NF-κB), nuclear factor E2-related factor 2 (Nrf2), and sterol regulatory element-binding protein (SREBF1) pathway in Madin-Darby bovine kidney (MDBK) cells, a widely used in vitro model in ruminant research...
June 14, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28623463/hypotonicity-induced-cell-swelling-activates-trpa1
#20
Fumitaka Fujita, Kunitoshi Uchida, Yasunori Takayama, Yoshiro Suzuki, Masayuki Takaishi, Makoto Tominaga
Hypotonic solutions can cause painful sensations in nasal and ocular mucosa through molecular mechanisms that are not entirely understood. We clarified the ability of human TRPA1 (hTRPA1) to respond to physical stimulus, and evaluated the response of hTRPA1 to cell swelling under hypotonic conditions. Using a Ca(2+)-imaging method, we found that modulation of AITC-induced hTRPA1 activity occurred under hypotonic conditions. Moreover, cell swelling in hypotonic conditions evoked single-channel activation of hTRPA1 in a cell-attached mode when the patch pipette was attached after cell swelling under hypotonic conditions, but not before swelling...
June 16, 2017: Journal of Physiological Sciences: JPS
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