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thapsigargin

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https://www.readbyqxmd.com/read/29315575/the-appswe-ps1a246e-mutations-in-an-astrocytic-cell-line-leads-to-increased-vulnerability-to-oxygen-and-glucose-deprivation-ca2-dysregulation-and-mitochondrial-abnormalities
#1
María Dolores Martin-de-Saavedra, Elisa Navarro, Ana J Moreno-Ortega, Mauricio P Cunha, Izaskun Buendia, Pablo Hernansanz-Agustín, Rafael León, María F Cano-Abad, Antonio Martínez-Ruiz, Ricardo Martínez-Murillo, Michael R Duchen, Manuela G López
Growing evidence suggests a close relationship between Alzheimer's Disease (AD) and cerebral hypoxia. Astrocytes play a key role in brain homeostasis and disease states, while some of the earliest changes in AD occur in astrocytes. We have therefore asked whether mutations associated with AD increase astrocyte vulnerability to ischemia. Two astroglioma cell lines derived from APPSWE /PS1A246E (APP, amyloid precursor protein; PS1, presenilin 1) transgenic mice and controls from normal mice were subjected to oxygen and glucose deprivation (OGD), an in vitro model of ischemia...
January 6, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29306759/il-4-and-serum-amyloid-p-inversely-regulate-fibrocyte-differentiation-by-targeting-store-operated-ca2-channels
#2
Jin-Nan Zhong, Lan Lan, Yi-Fei Chen, Ge Huang, Guang-Zhen He, Jiong Yang, Ya-Dong Gao
BACKGROUND: Circulating fibrocytes (CFs) have been shown to participate in subepithelial fibrosis of asthma with chronic airflow limitation by acting as an important source of fibroblasts deposited beneath airway epithelia. Serum amyloid P (SAP) is an innate inhibitor of fibrocytes differentiation. Store-operated Ca2+ entry (SOCE) is the major Ca2+ influx of non-excitable cells. In this study, the role of SOCE in the regulation of fibrocytes differentiation and the effects of Th2 cytokine IL-4 and SAP on SOCE of fibrocytes were investigated...
July 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29305424/regulation-of-gammaherpesvirus-lytic-replication-by-endoplasmic-reticulum-stress-induced-transcription-factors-atf4-and-chop
#3
Xing-Chen Zhou, Si-Han Dong, Zhong-Shun Liu, Shuai Liu, Chao-Can Zhang, Xiao-Zhen Liang
The stress-induced unfolded protein response (UPR) in the endoplasmic reticulum (ER) involves various signaling crosstalks and controls cell fate. B-cell receptor (BCR) signaling, which can trigger UPR, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo. However, how the UPR regulates BCR-mediated gammaherpesvirus infection is unknown. Here, we demonstrate that the ER stressors tunicamycin and thapsigargin inhibit BCR-mediated murine gammaherpesvirus 68 (MHV68) lytic replication by inducing expression of the UPR mediator Bip and blocking activation of Akt, ERK, and JNK...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29279319/survival-of-cancer-stem-like-cells-under-metabolic-stress-via-camk2%C3%AE-mediated-upregulation-of-sarco-endoplasmic-reticulum-calcium-atpase-expression
#4
Ki Cheong Park, Seung Won Kim, Jeong Yong Jeon, A Ra Jo, Hye Ji Choi, Jung Min Kim, Hyun Gyu Lee, Yonjung Kim, Gordon B Mills, Sung Hoon Noh, Min Goo Lee, Eun Sung Park, Jae-Ho Cheong
PURPOSE: Cancer cells grow in an unfavorable metabolic milieu in the tumor microenvironment and are constantly exposed to metabolic stress such as chronic nutrient depletion. Cancer stem-like cells (CSCs) are intrinsically resistant to metabolic stress, thereby surviving nutrient insufficiency and driving more malignant tumor progression. In this study, we aimed to demonstrate the potential mechanisms by which CSCs avoid Ca2+-dependent apoptosis during glucose deprivation. EXPERIMENTAL DESIGN: We investigated cell viability and apoptosis under glucose deprivation, performed genome-wide transcriptional profiling of paired CSCs and parental cells, studied the effect of calcium/calmodulin-dependent protein kinase 2 alpha (CaMK2α) gene knockdown, and investigated the role of nuclear factor kappa B (NFκB) in CSCs during time-dependent Ca2+-mediated and glucose deprivation-induced apoptosis...
December 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29248592/fluorochloridone-induces-primary-cultured-sertoli-cells-apoptosis-involvement-of-ros-and-intracellular-calcium-ions-mediated-erk1-2-activation
#5
Luqing Liu, Xiuli Chang, Yubin Zhang, Chunhua Wu, Rui Li, Liming Tang, Zhijun Zhou
Fluorochloridone (FLC) is a widely used pyrrolidone selective herbicide and reported to induce testis injuries in male rats, but the underlying mechanism is largely unknown. In the present study, primary-cultured Sertoli cells were exposed to FLC at the concentration of 0-10.00μM to study the mechanism of FLC-induced apoptosis. The roles of ROS, intracellular calcium, endoplasmic reticulum (ER), and ERK1/2 were looked at with ROS scavenger N-acetyl-cysteine (NAC), intracellular calcium chelator BAPTA-AM, ER calcium depleting agent thapsigargin (TG), and ERK1/2 inhibitor U0126, respectively...
December 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29246646/the-dialkyl-resorcinol-stemphol-disrupts-calcium-homeostasis-to-trigger-programmed-immunogenic-necrosis-in-cancer
#6
Seungwon Ji, Jin-Young Lee, Jan Schrör, Aloran Mazumder, Dong Man Jang, Sébastien Chateauvieux, Michael Schnekenburger, Che Ry Hong, Christo Christov, Hyoung Jin Kang, Youngjo Lee, Byung Woo Han, Kyu-Won Kim, Hee-Young Shin, Mario Dicato, Claudia Cerella, Gabriele M König, Barbora Orlikova, Marc Diederich
Stemphol (STP) is a novel druggable phytotoxin triggering mixed apoptotic and non-apoptotic necrotic-like cell death in human acute myeloid leukemia (AML). Use of several chemical inhibitors highlighted that STP-induced non-canonical programmed cell death was Ca2+-dependent but independent of caspases, poly (ADP-ribose) polymerase-1, cathepsin, or calpains. Similar to thapsigargin, STP led to increased cytosolic Ca2+ levels and computational docking confirmed binding of STP within the thapsigargin binding pocket of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA)...
December 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29246106/effects-of-methanol-and-formic-acid-on-human-platelet-aggregation
#7
Mikio Marumo, Ichiro Wakabayashi
BACKGROUND: Although ethanol is known to inhibit platelet aggregation, the effects of another variant of alcohol, methanol, have not been reported. The purpose of this study was to determine whether methanol and its metabolite, formic acid, affect Ca2+ entry into and subsequent aggregation of platelets in vitro. METHODS: Ca2+ entry into and aggregation of human platelets were measured by spectrofluorometry using Fura-2/AM as an indicator and the light transmission method, respectively...
December 16, 2017: Environmental Health and Preventive Medicine
https://www.readbyqxmd.com/read/29243095/ca2-camkk%C3%AE-pathway-is-required-for-adiponectin-induced-secretion-in-rat-submandibular-gland
#8
Chong Ding, Zhi-Hao Du, Sheng-Lin Li, Li-Ling Wu, Guang-Yan Yu
Adiponectin functions as a promoter of saliva secretion in rat submandibular gland via activation of adenosine monophosphate-activated protein kinase (AMPK) and increased paracellular permeability. Ca2+ mobilization is the primary signal for fluid secretion in salivary acinar cells. However, whether intracellular Ca2+ mobilization is involved in adiponectin-induced salivary secretion is unknown. Here, we found that full-length adiponectin (fAd) increased intracellular Ca2+ and saliva secretion in submandibular glands...
December 14, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29241198/fam3a-protects-against-glutamate-induced-toxicity-by-preserving-calcium-homeostasis-in-differentiated-pc12-cells
#9
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/29233021/amitriptyline-modulated-ca2-signaling-and-induced-ca2-independent-cell-viability-in-human-osteosarcoma-cells
#10
T Lu, C-T Chou, W-Z Liang, C-C Kuo, I-L Chen, J-L Wang, C-R Jan
Amitriptyline is a widely used tricyclic antidepressant, which acts primarily as a serotonin-norepinephrine reuptake inhibitor. This study examined the effect of amitriptyline on Ca2+ homeostasis and its related mechanism in MG63 human osteosarcoma cells. Amitriptyline evoked cytosolic-free Ca2+ concentrations ([Ca2+]i) rises concentration dependently. Amitriptyline-evoked Ca2+ entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. This entry was inhibited by Ca2+ entry modulators nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate but was not affected by the PKC inhibitor GF109203X...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29229760/functional-characterization-of-the-ca2-atpase-sma1-from-schistosoma-mansoni
#11
Xavier Maréchal, Ricardo De Mendonça, Roger Miras, Jean Revilloud, Patrice Catty
Schistosoma mansoni is a parasite that causes bilharzia, a neglected tropical disease affecting hundreds of millions of people each year worldwide. In 2012, S. mansoni had been identified as the only invertebrate possessing two SERCA-type Ca2+-ATPases, SMA1 and SMA2. However, our analysis of recent genomic data shows that the presence of two SERCA pumps is rather frequent in parasitic flatworms. To understand the reasons of this redundancy in S. mansoni , we compared SMA1 and SMA2 at different levels. In terms of sequence and organization, the genes SMA1 and SMA2 are similar, suggesting that they might be the result of a duplication event...
December 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29225183/ca2-mediates-axotomy-induced-necrosis-and-apoptosis-of-satellite-glial-cells-remote-from-the-transection-site-in-the-isolated-crayfish-mechanoreceptor
#12
Andrey Khaitin, Mikhail Rudkovskii, Anatoly Uzdensky
Severe nerve injury such as axotomy induces neuron degeneration and death of surrounding glial cells. Using a crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glia, we showed that axotomy not only mechanically injures glial cells at the transection location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. We studied Ca2+role in spontaneous or axotomy-induced death of remote glial cells. Stretch receptors were isolated using the original technique that kept the neuron connected to the ventral cord ganglion (control preparations)...
December 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29215706/map-and-correlate-intracellular-calcium-response-and-matrix-deposition-in-cartilage-under-physiological-oxygen-tensions
#13
Jin Zhou, Danyang Yue, Yuying Bai, Fei Kong, Jun Pan
Face to the limited repair capability of cartilage, we intended to find out signaling responsible for its matrix synthesis. Since spontaneous calcium response likes a label of cell status, here it was mapped in fresh and 24 h cultured in situ chondrocytes under oxygen tensions of 20%, 5% and 1% as well as mimic hypoxia conditions. The calcium source was traced using ethylene glycol-bis (β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and thapsigargin (TG) to treat cartilage. Their relative matrix of type II collagen (COLL-II) and glycosaminoglycan (GAG) were quantified after cultured for three and seven days...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29206294/hormone-regulates-endometrial-function-via-cooperation-of-endoplasmic-reticulum-stress-and-mtor-autophagy
#14
Diqi Yang, Tingting Jiang, Jianguo Liu, Jin Hong, Pengfei Lin, Huatao Chen, Dong Zhou, Keqiong Tang, Aihua Wang, Yaping Jin
In ruminant, the receptive endometrium and the elongation of the hatched blastocyst are required to complete the process of implantation. However, the mechanisms regulating goat endometrial function during the peri-implantation period of pregnancy are still unclear. In this study, EECs were treated with progesterone, estradiol and interferon-tau (IFNT). We have found that endoplasmic reticulum (ER) stress were activated under hormones treatment. To identify the cellular mechanism of regulation of endometrial function, we investigated the effect of ER stress activator thapsigargin (TG) and inhibitor 4 phenyl butyric acid (4-PBA) on EECs...
December 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29201062/comparative-analysis-of-spontaneous-and-stimulus-evoked-calcium-transients-in-proliferating-and-differentiating-human-midbrain-derived-stem-cells
#15
Torben Johansen, Christina Krabbe, Sissel Ida Schmidt, Alberto Martínez Serrano, Morten Meyer
Spontaneous cytosolic calcium transients and oscillations have been reported in various tissues of nonhuman and human origin but not in human midbrain-derived stem cells. Using confocal microfluorimetry, we studied spontaneous calcium transients and calcium-regulating mechanisms in a human ventral mesencephalic stem cell line undergoing proliferation and neuronal differentiation. Spontaneous calcium transients were detected in a large fraction of both proliferating (>50%) and differentiating (>55%) cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29193528/-epicatechin-induced-relaxation-of-isolated-human-saphenous-vein-roles-of-k-and-ca2-channels
#16
Marija Marinko, Goran Jankovic, Dragoslav Nenezic, Predrag Milojevic, Ivan Stojanovic, Vladimir Kanjuh, Aleksandra Novakovic
In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin...
November 29, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29170452/liraglutide-restores-chronic-er-stress-autophagy-impairments-and-apoptotic-signalling-in-sh-sy5y-cells
#17
Theodora Panagaki, Maria Michael, Christian Hölscher
Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer's disease patients showed improvements in cerebral glucose consumption that signifies disease progression. However, the exact underlying mechanism of action remains unclear. Chronic endoplasmic reticulum (ER) stress has recently emerged as a mechanism for neuronal injury, rendering it a potent therapeutic target for acute and chronic neurodegenerative disorders...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29159836/mechanisms-of-calcium-sequestration-by-isolated-malpighian-tubules-of-the-house-cricket-acheta-domesticus
#18
Austin Browne, Michael J O'Donnell
Hemolymph calcium homeostasis in insects is achieved by the Malpighian tubules, primarily by sequestering excess Ca(2+) within internal calcium stores (Ca-rich granules) most often located within type I (principal) tubule cells. Using both the scanning ion-selective electrode technique and the Ramsay secretion assay this study provides the first measurements of basolateral and transepithelial Ca(2+) fluxes across the Malpighian tubules of an Orthopteran insect, the house cricket Acheta domesticus. Ca(2+) transport was specific to midtubule segments, where 97% of the Ca(2+) entering the tubule is sequestered within intracellular calcium stores and the remaining 3% is secreted into the lumen...
November 21, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29158376/leukemia-specific-delivery-of-mutant-notch1-targeted-therapy
#19
Giovanni Roti, Jun Qi, Samuel Kitara, Marta Sanchez-Martin, Amy Saur Conway, Anthony C Varca, Angela Su, Lei Wu, Andrew L Kung, Adolfo A Ferrando, James E Bradner, Kimberly Stegmaier
On-target drug delivery remains a challenge in cancer precision medicine; it is difficult to deliver a targeted therapy to cancer cells without incurring toxicity to normal tissues. The SERCA (sarco-endoplasmic reticulum Ca2+ ATPase) inhibitor thapsigargin inhibits mutant NOTCH1 receptors compared with wild type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic in humans. Leveraging the addiction of ALL to folic acid, we conjugated folate to an alcohol derivative of thapsigargin via a cleavable ester linkage...
November 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29154934/cephalostatin-1-analogues-activate-apoptosis-via-the-endoplasmic-reticulum-stress-signaling-pathway
#20
Lubna H Tahtamouni, Mansour M Nawasreh, Zainab A Al-Mazaydeh, Rema A Al-Khateeb, Reem N Abdellatif, Randa M Bawadi, James R Bamburg, Salem R Yasin
The current study was conducted to compare the cytotoxicity of two stereospecific cephalostatin 1 analogues (CAs) against several human normal cell types and cancer cell lines and to determine their cytotoxic mechanism. Both CA analogues induced apoptosis and were cytotoxic with 50% growth inhibition (GI50) at ~1µM or less in six human cancer cell lines but neither analogue at 10µM killed more than 14% of any of three types of normal human cells suggesting their cytotoxicity is cancer-specific. CA treatment inhibited clonogenic tumor growth and activated caspase 3 and 9 but not caspase 8...
November 15, 2017: European Journal of Pharmacology
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