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https://www.readbyqxmd.com/read/29348267/toll-like-receptor-9-dependent-ampk%C3%AE-activation-occurs-via-tak1-and-contributes-to-rhoa-rock-signaling-and-actin-polymerization-in-vascular-smooth-muscle-cells
#1
Cameron G McCarthy, Camilla Ferreira Wenceslau, Safia Ogbi, Theodora Szasz, R Clinton Webb
Traditionally, Toll-like receptor (TLR)9 signals through a MyD88-dependent cascade that results in pro-inflammatory gene transcription. Recently it was reported that TLR9 also participates in a stress tolerance signaling cascade in non-immune cells. In this non-canonical pathway, TLR9 binds to and inhibits sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), modulating intracellular calcium handling, and subsequently resulting in the activation of 5'-AMP-activated protein kinase (AMPK)α. We have previously reported TLR9 causes increased contraction in isolated arteries; however, the mechanisms underlying this vascular dysfunction need to be further clarified...
January 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29345355/effects-of-antioxidants-on-apoptosis-induced-by-dasatinib-and-nilotinib-in-k562-cells
#2
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/29337094/vitamin-d-attenuates-pressure-overload-induced-cardiac-remodeling-and-dysfunction-in-mice
#3
Liang Zhang, Xiao Yan, Jie Bai, Tesfaldet Habtemariam Hidru, Qing-Shan Wang, Hui-Hua Li
Vitamin D (VD) and its analogues play critical roles in metabolic and cardiovascular diseases. Recent studies have demonstrated that VD exerts a protective role in cardiovascular diseases. However, the beneficial effect of VD on pressure overload-induced cardiac remodeling and dysfunction and its underlying mechanisms are not fully elucidated. In this study, cardiac dysfunction and hypertrophic remodeling in mice were induced by pressure overload. Cardiac function was evaluated by echocardiography, and myocardial histology was detected by H&E and Masson's trichrome staining...
January 11, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29316265/effects-of-chronic-hypoxia-on-diaphragm-function-in-deer-mice-native-to-high-altitude
#4
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/29288034/structural-and-functional-remodelling-of-the-atrioventricular-node-with-ageing-in-rats-the-role-of-hyperpolarization-activated-cyclic-nucleotide-gated-and-ryanodine-2-channels
#5
Yawer Saeed, Ian Temple, Zoltan Borbas, Andrew Atkinson, Joseph Yanni, Michal Maczewski, Urszula Mackiewicz, Mariam Aly, Sunil J R J Logantha, Clifford Garratt, Halina Dobrzynski
BACKGROUND: Ageing is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVES: The aim of the study is to identify the structural and functional remodelling in the atrioventricular junction (AVJ) with ageing. METHODS: Electrophysiological, histology and immunohistochemistry experiments on male Wistar-Hanover rats aged 3months (n=24) and 2years (n=15) were performed. AH interval, Wenkebach cycle length (WBCL) and AVN effective refractory period (AVNERP) were measured...
December 26, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
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
#6
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
#7
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/29273502/mir-25-tough-decoy-enhances-cardiac-function-in-heart-failure
#8
Dongtak Jeong, Jimeen Yoo, Philyoung Lee, Sacha V Kepreotis, Ahyoung Lee, Christine Wahlquist, Brian D Brown, Changwon Kho, Mark Mercola, Roger J Hajjar
MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery...
November 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29249393/therapeutic-benefit-and-gene-network-regulation-by-combined-gene-transfer-of-apelin-fgf2-and-serca2a-into-ischemic-heart
#9
Edith Renaud-Gabardos, Florence Tatin, Fransky Hantelys, Benoît Lebas, Denis Calise, Oksana Kunduzova, Bernard Masri, Françoise Pujol, Pierre Sicard, Philippe Valet, Jérôme Roncalli, Xavier Chaufour, Barbara Garmy-Susini, Angelo Parini, Anne-Catherine Prats
Despite considerable advances in cardiovascular disease treatment, heart failure remains a public health challenge. In this context, gene therapy appears as an attractive approach, but clinical trials using single therapeutic molecules result in moderate benefit. With the objective of improving ischemic heart failure therapy, we designed a combined treatment, aimed to simultaneously stimulate angiogenesis, prevent cardiac remodeling, and restore contractile function. We have previously validated IRES-based vectors as powerful tools to co-express genes of interest...
November 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29246646/the-dialkyl-resorcinol-stemphol-disrupts-calcium-homeostasis-to-trigger-programmed-immunogenic-necrosis-in-cancer
#10
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
#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/29229678/epitope-mapping-of-serca2a-identifies-an-antigenic-determinant-that-induces-mainly-atrial-myocarditis-in-a-j-mice
#12
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
#13
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/29208771/advanced-iron-overload-cardiomyopathy-in-a-genetic-murine-model-is-rescued-by-resveratrol-therapy
#14
Subhash K Das, Pavel Zhabyeyev, Ratnadeep Basu, Vaibhav B Patel, Jason R B Dyck, Zamaneh Kassiri, Gavin Y Oudit
Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major co-morbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid pre-clinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin knockout (HJVKO) mice, which lack hemojuvelin (HJV), a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high iron diet starting at 4 weeks of age for a duration of 1 year...
December 5, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29193756/investigating-the-cardiac-pathology-of-sco2-mediated-hypertrophic-cardiomyopathy-using-patients-induced-pluripotent-stem-cell-derived-cardiomyocytes
#15
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
#16
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/29191788/progressive-impairment-of-atrial-myocyte-function-during-left-ventricular-hypertrophy-and-heart-failure
#17
Florentina Pluteanu, Yulia Nikonova, Anna Holzapfel, Birgit Herzog, Anna Scherer, Judit Preisenberger, Jelena Plačkić, Katharina Scheer, Teodora Ivanova, Alicja Bukowska, Andreas Goette, Jens Kockskämper
Hypertensive heart disease (HHD) can cause left ventricular (LV) hypertrophy and heart failure (HF). It is unclear, though, which factors may contribute to the transition from compensated LV hypertrophy to HF in HHD. We hypothesized that maladaptive atrial remodeling with impaired atrial myocyte function would occur in advanced HHD and may be associated with the emergence of HF. Experiments were performed on atrial myocytes and tissue from old (15-25months) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with advanced HHD...
November 27, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29185184/changes-in-contractile-and-metabolic-parameters-of-skeletal-muscle-as-rats-age-from-3-to-12-months
#18
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/29179218/puerarin-enhances-ca2-reuptake-and-ca2-content-of-sarcoplasmic-reticulum-in-murine-embryonic-stem-cell-derived-cardiomyocytes-via-upregulation-of-serca2a
#19
Lu Wang, Yurong Cui, Qinghua Liu, Yuanlong Song, Qinghua Hu, Ming Tang, Jürgen Hescheler, Jiaoya Xi
BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as potential sources for cardiac regenerative therapy. However, the immature sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this report, we examined the effect of puerarin, an isoflavone compound, on SR function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body-based differentiation method. Confocal calcium imaging and whole-cell patch clamps were performed to assess the function of SR...
November 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29178440/invisible-detergents-for-structure-determination-of-membrane-proteins-by-small-angle-neutron-scattering
#20
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
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