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https://www.readbyqxmd.com/read/29345355/effects-of-antioxidants-on-apoptosis-induced-by-dasatinib-and-nilotinib-in-k562-cells
#1
Sara Damiano, Serena Montagnaro, Maria Valeria Puzio, Lorella Severino, Ugo Pagnini, Marcella Barbarino, Daniele Cesari, Antonio Giordano, Salvatore Florio, Roberto Ciarcia
In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation and apoptosis...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29316265/effects-of-chronic-hypoxia-on-diaphragm-function-in-deer-mice-native-to-high-altitude
#2
Neal J Dawson, Sulayman A Lyons, Danielle A Henry, Graham R Scott
AIM: We examined the effects of chronic hypoxia on diaphragm function in high- and low-altitude populations of Peromyscus mice. METHODS: Deer mice (P. maniculatus) native to high altitude and congeneric mice native to low altitude (P. leucopus) were born and raised in captivity to adulthood, and were acclimated to normoxia or hypobaric hypoxia (12 or 9 kPa, simulating hypoxia at 4300 m and 7000 m) for 6-8 weeks. We then measured indices of mitochondrial respiration capacity, force production, and fatigue resistance in the diaphragm...
January 9, 2018: Acta Physiologica
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
#3
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/29273673/reduced-serca-activity-underlies-dysregulation-of-ca2-homeostasis-under-atmospheric-o2-levels
#4
Thomas P Keeley, Richard C M Siow, Ron Jacob, Giovanni E Mann
Unregulated increases in cellular Ca2+ homeostasis are a hallmark of pathophysiological conditions and a key trigger of cell death. Endothelial cells cultured under physiologic O2 conditions (5% O2) exhibit a reduced cytosolic Ca2+ response to stimulation. The mechanism for reduced plateau [Ca2+]i upon stimulation was due to increased sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)-mediated reuptake rather than changes in Ca2+ influx capacity. Agonist-stimulated phosphorylation of the SERCA regulatory protein phospholamban was increased in cells cultured under 5% O2 Elevation of cytosolic and mitochondrial [Ca2+] and cell death after prolonged ionomycin treatment, as a model of Ca2+ overload, were lower when cells were cultured long-term under 5% compared with 18% O2 This protection was abolished by cotreatment with the SERCA inhibitor cyclopiazonic acid...
December 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29246646/the-dialkyl-resorcinol-stemphol-disrupts-calcium-homeostasis-to-trigger-programmed-immunogenic-necrosis-in-cancer
#5
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/29229760/functional-characterization-of-the-ca2-atpase-sma1-from-schistosoma-mansoni
#6
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/29229678/epitope-mapping-of-serca2a-identifies-an-antigenic-determinant-that-induces-mainly-atrial-myocarditis-in-a-j-mice
#7
Bharathi Krishnan, Chandirasegaran Massilamany, Rakesh H Basavalingappa, Arunakumar Gangaplara, Rajkumar A Rajasekaran, Muhammad Z Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S Nandi, Paras K Mishra, Raymond A Sobel, Jennifer L Strande, David Steffen, Jay Reddy
Sarcoplasmic/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29228618/calcium-homeostasis-and-endoplasmic-reticulum-stress-are-involved-in-salvianolic-acid-b-offered-protection-against-cardiac-toxicity-of-arsenic-trioxide
#8
Jing-Yi Zhang, Bin Zhang, Min Wang, Wei Wang, Ping Liao, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is a potent anticancer agent used to treat acute promyelocytic leukemia. However, its cardiotoxicity limits ATO's widespread clinical use. Previous studies demonstrated that ATO may aggravate Ca2+ overload and promote endoplasmic reticulum stress (ERS). Salvianolic acid B (Sal B) is cardioprotective against ATO and enhances ATO's anticancer activities. The present study assessed whether the Sal B protective effect was related to maintenance of Ca2+ homeostasis and inhibition of ER stress...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29193756/investigating-the-cardiac-pathology-of-sco2-mediated-hypertrophic-cardiomyopathy-using-patients-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Tova Hallas, Binyamin Eisen, Yuval Shemer, Ronen Ben Jehuda, Lucy N Mekies, Shulamit Naor, Revital Schick, Sivan Eliyahu, Irina Reiter, Eugene Vlodavsky, Yeshayahu Shai Katz, Katrin Õunap, Avraham Lorber, Richard Rodenburg, Hanna Mandel, Mihaela Gherghiceanu, Ofer Binah
Mutations in SCO2 are among the most common causes of COX deficiency, resulting in reduced mitochondrial oxidative ATP production capacity, often leading to hypertrophic cardiomyopathy (HCM). To date, none of the recent pertaining reports provide deep understanding of the SCO2 disease pathophysiology. To investigate the cardiac pathology of the disease, we were the first to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) from SCO2-mutated patients. For iPSC generation, we reprogrammed skin fibroblasts from two SCO2 patients and healthy controls...
November 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29192360/hyperglycemia-induced-cardiac-contractile-dysfunction-in-the-diabetic-heart
#10
REVIEW
Raphael M Singh, Tahreem Waqar, Frank C Howarth, Ernest Adeghate, Keshore Bidasee, Jaipaul Singh
The development of a diabetic cardiomyopathy is a multifactorial process, and evidence is accumulating that defects in intracellular free calcium concentration [Ca2+]i or its homeostasis are related to impaired mechanical performance of the diabetic heart leading to a reduction in contractile dysfunction. Defects in ryanodine receptor, reduced activity of the sarcoplasmic reticulum calcium pump (SERCA) and, along with reduced activity of the sodium-calcium exchanger (NCX) and alterations in myofilament, collectively cause a calcium imbalance within the diabetic cardiomyocytes...
December 1, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/29185184/changes-in-contractile-and-metabolic-parameters-of-skeletal-muscle-as-rats-age-from-3-to-12-months
#11
Hongyang Xu, Graham D Lamb, Robyn M Murphy
Laboratory rats are considered mature at 3 months despite that musculoskeletal growth is still occurring. Changes in muscle physiological and biochemical characteristics during development from 3 months, however, are not well understood. Whole muscles and single skinned fibres from fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus (SOL) muscles were examined from male Sprague-Dawley rats (3, 6, 9, 12 months). Ca2+ sensitivity of contractile apparatus decreased with age in both fast- (~ 0...
November 28, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/29178440/invisible-detergents-for-structure-determination-of-membrane-proteins-by-small-angle-neutron-scattering
#12
Søren Roi Midtgaard, Tamim A Darwish, Martin Cramer Pedersen, Pie Huda, Andreas Haahr Larsen, Grethe Vestergaard Jensen, Søren Andreas Røssel Kynde, Nicholas Skar-Gislinge, Agnieszka Janina Zygadlo Nielsen, Claus Olesen, Mickael Blaise, Jerzy Józef Dorosz, Thor Seneca Thorsen, Raminta Venskutonytė, Christian Krintel, Jesper V Møller, Henrich Frielinghaus, Elliot Paul Gilbert, Anne Martel, Jette Sandholm Kastrup, Poul Erik Jensen, Poul Nissen, Lise Arleth
A novel and generally applicable method for determining structures of membrane proteins in solution via small-angle neutron scattering (SANS) is presented. Common detergents for solubilizing membrane proteins were synthesized in isotope-substituted versions for utilizing the intrinsic neutron scattering length difference between hydrogen and deuterium. Individual hydrogen/deuterium levels of the detergent head and tail groups were achieved such that the formed micelles became effectively invisible in heavy water (D2 O) when investigated by neutrons...
November 27, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29176668/a-protein-interaction-mechanism-for-suppressing-the-mechanosensitive-piezo-channels
#13
Tingxin Zhang, Shaopeng Chi, Fan Jiang, Qiancheng Zhao, Bailong Xiao
Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29170642/muscle-non-shivering-thermogenesis-and-its-role-in-the-evolution-of-endothermy
#14
REVIEW
Julia Nowack, Sylvain Giroud, Walter Arnold, Thomas Ruf
The development of sustained, long-term endothermy was one of the major transitions in the evolution of vertebrates. Thermogenesis in endotherms does not only occur via shivering or activity, but also via non-shivering thermogenesis (NST). Mammalian NST is mediated by the uncoupling protein 1 in the brown adipose tissue (BAT) and possibly involves an additional mechanism of NST in skeletal muscle. This alternative mechanism is based on Ca(2+)-slippage by a sarcoplasmatic reticulum Ca(2+)-ATPase (SERCA) and is controlled by the protein sarcolipin...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29168286/comparative-proteomic-profiling-reveals-a-role-for-cisd2-in-skeletal-muscle-aging
#15
Yi-Long Huang, Zhao-Qing Shen, Chia-Yu Wu, Yuan-Chi Teng, Chen-Chung Liao, Cheng-Heng Kao, Liang-Kung Chen, Chao-Hsiung Lin, Ting-Fen Tsai
Skeletal muscle has emerged as one of the most important tissues involved in regulating systemic metabolism. The gastrocnemius is a powerful skeletal muscle composed of predominantly glycolytic fast-twitch fibers that are preferentially lost among old age. This decrease in gastrocnemius muscle mass is remarkable during aging; however, the underlying molecular mechanism is not fully understood. Strikingly, there is a ~70% decrease in Cisd2 protein, a key regulator of lifespan in mice and the disease gene for Wolfram syndrome 2 in humans, within the gastrocnemius after middle age among mice...
November 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/29158376/leukemia-specific-delivery-of-mutant-notch1-targeted-therapy
#16
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/29157865/peptide-yy-3-36-modulates-intracellular-calcium-through-activation-of-the-phosphatidylinositol-pathway-in-hippocampal-neurons
#17
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/29155350/the-pmca-pumps-in-genetically-determined-neuronal-pathologies
#18
REVIEW
Tito Calì, Marisa Brini, Ernesto Carafoli
Ca(2+) signals regulate most aspects of animal cell life. They are of particular importance to the nervous system, in which they regulate specific functions, from neuronal development to synaptic plasticity. The homeostasis of cell Ca(2+) must thus be very precisely regulated: in all cells Ca(2+) pumps transport it from the cytosol to the extracellular medium (the Plasma Membrane Ca(2+) ATPases, hereafter referred to as PMCA pumps) or to the lumen of intracellular organelles (the Sarco/Endoplasmatic Reticulum Ca(2+) ATPase and the Secretory Pathway Ca(2+) ATPase, hereafter referred to as SERCA and SPCA pumps, respectively)...
November 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29145427/do-microplastic-particles-affect-daphnia-magna-at-the-morphological-life-history-and-molecular-level
#19
Hannes K Imhof, Jakub Rusek, Michaela Thiel, Justyna Wolinska, Christian Laforsch
Microplastic particles are ubiquitous not only in marine but also in freshwater ecosystems. However, the impacts of microplastics, consisting of a large variety of synthetic polymers, on freshwater organisms remains poorly understood. We examined the effects of two polymer mixtures on the morphology, life history and on the molecular level of the waterflea Daphnia magna (three different clones). Microplastic particles of ~40 μm were supplied at a low concentration (1% of the food particles) leading to an average of ~30 particles in the digestive tract which reflects a high microplastic contamination but still resembles a natural situation...
2017: PloS One
https://www.readbyqxmd.com/read/29133865/cold-acclimation-causes-fiber-type-specific-responses-in-glucose-and-fat-metabolism-in-rat-skeletal-muscles
#20
Diane M Sepa-Kishi, Yass Sotoudeh-Nia, Ayesha Iqbal, George Bikopoulos, Rolando B Ceddia
This study investigated fiber type-specific metabolic responses and the molecular mechanisms that regulate glucose and fat metabolism in oxidative and glycolytic muscles upon cold acclimation. Male Wistar rats were exposed to cold (4 °C) for 7 days, and then glycogen synthesis and content, glucose and palmitate oxidation, and the molecular mechanisms underlying these metabolic pathways were assessed in soleus (Sol), extensor digitorum longus (EDL), and epitrochlearis (Epit) muscles. Cold acclimation increased glycogen synthesis, glycogen content, glucose oxidation, and reduced glycogen synthase (GS) phosphorylation only in Sol muscles...
November 13, 2017: Scientific Reports
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