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https://www.readbyqxmd.com/read/28906486/small-molecule-rl71-triggered-excessive-autophagic-cell-death-as-a-potential-therapeutic-strategy-in-triple-negative-breast-cancer
#1
Jian Gao, Minmin Fan, Shuang Peng, Minxia Zhang, Gang Xiang, Xin Li, Wenjie Guo, Yang Sun, Xuefeng Wu, Xudong Wu, Guang Liang, Yan Shen, Qiang Xu
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca(2+) from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28903365/protective-effects-of-circulating-microvesicles-derived-from-myocardial-ischemic-rats-on-apoptosis-of-cardiomyocytes-in-myocardial-ischemia-reperfusion-injury
#2
Yao Wang, Su Wei, Yi-Lu Wang, Miao Liu, Man Shang, Qi Zhang, Yan-Na Wu, Ming-Lin Liu, Jun-Qiu Song, Yan-Xia Liu
OBJECTIVE: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28884444/the-ccaat-box-in-the-proximal-serca2-gene-promoter-regulates-basal-and-stress-induced-transcription-in-cardiomyocytes
#3
Jorge Fragoso-Medina, Gabriela Rodriguez, Angel Zarain-Herzberg
The cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated...
September 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28819266/amalaki-rasayana-a-traditional-indian-drug-enhances-cardiac-mitochondrial-and-contractile-functions-and-improves-cardiac-function-in-rats-with-hypertrophy
#4
Vikas Kumar, Kumar A Aneesh, K Kshemada, Kumar G S Ajith, Raj S S Binil, Neha Deora, G Sanjay, A Jaleel, T S Muraleedharan, E M Anandan, R S Mony, M S Valiathan, Kumar T R Santhosh, C C Kartha
We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801239/salsalate-activates-skeletal-muscle-thermogenesis-and-protects-mice-from-high-fat-diet-induced-metabolic-dysfunction
#5
Li Nie, Xin-Lu Yuan, Ke-Tao Jiang, Yu-Hui Jiang, Jin Yuan, Lan Luo, Shi-Wei Cui, Cheng Sun
Salsalate plays beneficial roles for ameliorating hyperglycemia and dyslipidemia in type 2 diabetes patients, but the underlying mechanisms are still poorly understood. In this study, by administering salsalate to mice fed with high fat diet and examining how salsalate rectifies metabolic dysfunction in these obese mice, we found that salsalate stimulated body temperature and attenuated body weight gain without affecting food intake. Our results showed that salsalate application decreased lipid accumulation in liver and epididymal white adipose tissue (eWAT), inhibited hepatic gluconeogenesis and improved insulin signaling transduction in eWAT...
August 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28765908/serca1-attenuates-diaphragm-relaxation-and-uptake-rate-of-serca-in-rats-with-acute-sepsis
#6
Jianyou Zhang, Hui Liu, Shitong Li, Jin Wu, Jianhong Sun
The present study aimed to investigate the effects of acute sepsis on diaphragm contractility and relaxation, via examining the Ca2+‑uptake function of sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA), and the protein levels of SERCA1, SERCA2 and the ryanodine receptor (RyR) of the sarcoplasmic reticulum (SR). A sepsis rat model was established through cecal ligation and puncture (CLP). A total of 6 and 12 h following CLP, the isometric contractile and relaxation parameters of the diaphragm were measured...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28761152/astragaloside-iv-protects-against-podocyte-injury-via-serca2-dependent-er-stress-reduction-and-ampk%C3%AE-regulated-autophagy-induction-in-streptozotocin-induced-diabetic-nephropathy
#7
Hengjiang Guo, Yi Wang, Xuemei Zhang, Yingjun Zang, Yang Zhang, Li Wang, Hao Wang, Yunman Wang, Aili Cao, Wen Peng
Aberrant endoplasmic reticulum (ER) stress and autophagy are associated with diabetic nephropathy. Here we investigated the effect of astragaloside IV (AS-IV) on the progression of diabetic nephropathy (DN) and the underlying mechanism involving ER stress and autophagy in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-incubated podocytes. The diabetic mice developed progressive albuminuria and glomerulosclerosis within 8 weeks, which were significantly ameliorated by AS-IV treatment in a dose-dependent manner...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724751/tomo-seq-identifies-sox9-as-a-key-regulator-of-cardiac-fibrosis-during-ischemic-injury
#8
Grégory P A Lacraz, Jan Philipp Junker, Monika M Gladka, Bas Molenaar, Koen T Scholman, Marta Vigil-Garcia, Danielle Versteeg, Hesther de Ruiter, Marit W Vermunt, Menno P Creyghton, Manon M H Huibers, Nicolaas de Jonge, Alexander van Oudenaarden, Eva van Rooij
Background -Cardiac ischemic injury induces a pathological remodeling response, which can ultimately lead to heart failure. Detailed mechanistic insights into molecular signaling pathways relevant for different aspects of cardiac remodeling will support the identification of novel therapeutic targets. Methods -While genome-wide transcriptome analysis on diseased tissues has greatly advanced our understanding of the regulatory networks that drive pathological changes in the heart, this approach has been disadvantaged by the fact that the signals are derived from tissue homogenates...
July 19, 2017: Circulation
https://www.readbyqxmd.com/read/28698769/high-intensity-exercise-reduces-cardiac-fibrosis-and-hypertrophy-but-does-not-restore-the-nitroso-redox-imbalance-in-diabetic-cardiomyopathy
#9
Ulises Novoa, Diego Arauna, Marisol Moran, Madelaine Nuñez, Sebastián Zagmutt, Sergio Saldivia, Cristian Valdes, Jorge Villaseñor, Carmen Gloria Zambrano, Daniel R Gonzalez
Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28651627/induction-of-endoplasmic-reticulum-calcium-pump-expression-during-early-leukemic-b-cell-differentiation
#10
Lamia Aït Ghezali, Atousa Arbabian, Hervé Roudot, Jean-Philippe Brouland, Fanny Baran-Marszak, Evelyn Salvaris, Andrew Boyd, Hans G Drexler, Agnes Enyedi, Remi Letestu, Nadine Varin-Blank, Bela Papp
BACKGROUND: Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis...
June 26, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28630914/deregulated-ca-2-cycling-underlies-the-development-of-arrhythmia-and-heart-disease-due-to-mutant-obscurin
#11
Li-Yen R Hu, Maegen A Ackermann, Peter A Hecker, Benjamin L Prosser, Brendan King, Kelly A O'Connell, Alyssa Grogan, Logan C Meyer, Christopher E Berndsen, Nathan T Wright, W Jonathan Lederer, Aikaterini Kontrogianni-Konstantopoulos
Obscurins are cytoskeletal proteins with structural and regulatory roles encoded by OBSCN. Mutations in OBSCN are associated with the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Specifically, the R4344Q mutation present in immunoglobulin domain 58 (Ig58) was the first to be linked with the development of HCM. To assess the effects of R4344Q in vivo, we generated the respective knock-in mouse model. Mutant obscurins are expressed and incorporated normally into sarcomeres...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28612341/cardiomyocyte-marker-expression-in-dogs-with-left-atrial-enlargement-due-to-dilated-cardiomyopathy-or-myxomatous-mitral-valve-disease
#12
Izabela Janus, Malgorzata Kandefer-Gola, Rafal Ciaputa, Agnieszka Noszczyk-Nowak, Urszula Paslawska, Massimiliano Tursi, Marcin Nowak
INTRODUCTION: Dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD) are common heart conditions in dogs. They have different etiology and pathogenesis and although other studies focused on changes in the left ventricles of the affected hearts, the aim of our study was to assess the expressions of some intrinsic proteins in the enlarged left atria. MATERIAL AND METHODS: We performed an immunohistochemical analysis of left atrial specimens obtained from 15 dogs with DCM, 35 dogs with MMVD and six control dogs...
June 14, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28558076/functional-effects-of-hyperthyroidism-on-cardiac-papillary-muscle-in-rats
#13
Fabricio Furtado Vieira, Robson Ruiz Olivoto, Priscyla Oliveira da Silva, Julio Cesar Francisco, Rosalvo Tadeu Hochmuller Fogaça
BACKGROUND: Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. OBJECTIVES: To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. METHODS: We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection...
December 2016: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28543734/the-effect-of-repeated-periods-of-speed-endurance-training-on-performance-running-economy-and-muscle-adaptations-113-120-characters
#14
Casper Skovgaard, Nicki Winfield Almquist, Jens Bangsbo
The effect of repeated intense training interventions was investigated in eight trained male runners (maximum oxygen uptake (VO2 -max): 59.3±3.2 ml·kg(-1) ·min(-1) , mean±SD) who performed ten speed endurance training (SET; repeated 30-s 'all-out' bouts) and ten aerobic moderate-intensity training sessions during two 40-day periods (P1 and P2) separated by ~80 days of habitual training. Before and after both P1 and P2, subjects completed an incremental test to exhaustion to determine VO2 -max and a repeated running test at 90% vVO2 -max to exhaustion (RRT) to determine short-term endurance capacity...
May 19, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28533073/the-impact-of-sevoflurane-on-coupling-of-the-left-ventricular-to-systemic-vasculature-in-rats-with-chronic-pulmonary-hypertension
#15
Lu Wang, Hui Luo, Gang Qin, Yanan Cao, Xiaowei Gao, Zhong Zhang, Zhi Ye, Junjie Zhang, Qulian Guo, E Wang
OBJECTIVES: The relationship between left ventricular function and afterload has not been investigated as much as the right ventricular function under chronic pulmonary hypertension (PH) during anesthesia. This study was designed to investigate effects of sevoflurane on the intrinsic coupling relationship between the left ventricle and systemic vasculature in the presence of PH. DESIGN: A randomized, controlled study. SETTING: University hospital...
February 13, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28500853/protective-effects-of-circulating-microvesicles-derived-from-myocardial-ischemic-rats-on-apoptosis-of-cardiomyocytes-in-myocardial-ischemia-reperfusion-injury
#16
Yao Wang, Su Wei, Yi-Lu Wang, Miao Liu, Man Shang, Qi Zhang, Yan-Na Wu, Ming-Lin Liu, Jun-Qiu Song, Yan-Xia Liu
OBJECTIVE: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487373/interactions-between-small-ankyrin-1-and-sarcolipin-coordinately-regulate-activity-of-the-sarco-endo-plasmic-reticulum-ca-2-atpase-serca1
#17
Patrick F Desmond, Amanda Labuza, Joaquin Muriel, Michele L Markwardt, Allison E Mancini, Mark A Rizzo, Robert J Bloch
SERCA1, the sarco(endo)plasmic reticulum Ca(2+)-ATPase of skeletal muscle, is essential for muscle relaxation and maintenance of low resting Ca(2+) levels in the myoplasm. We recently reported that small ankyrin 1 (sAnk1) interacts with the sarco(endo)plasmic reticulum Ca(2+)-ATPase in skeletal muscle (SERCA1) to inhibit its activity. We also showed that this interaction is mediated at least in part through sAnk1's transmembrane domain in a manner similar to that of sarcolipin (SLN). Earlier studies have shown that SLN and phospholamban, the other well studied small SERCA-regulatory proteins, oligomerize either alone or together...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28486663/ca2-signaling-machinery-is-present-at-intercellular-junctions-and-structures-associated-with-junction-turnover-in-rat-sertoli-cells
#18
Kevin Lyon, Arlo Adams, Matthew Piva, Parisa Asghari, Edwin D Moore, A Wayne Vogl
The endoplasmic reticulum (ER) in Sertoli cells is a component of unique adhesion junctions (ectoplasmic specializations-ESs) and is closely associated with structures termed tubulobulbar complexes (TBCs) that internalize intercellular junctions during sperm release and during the translocation of spermatocytes through the blood-testis barrier. A role for the ER in Ca2+ regulation at ESs and TBCs has been suspected, but evidence for this function has proved elusive. Using electron microscopy, we define two new ER-plasma membrane (PM) contact sites in apical Sertoli cell processes...
June 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28472418/increased-passive-stiffness-promotes-diastolic-dysfunction-despite-improved-ca2-handling-during-left-ventricular-concentric-hypertrophy
#19
Åsmund T Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A Linke, Håvard E Danielsen, Ole M Sejersted, Ivar Sjaastad, William E Louch
Aims: Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28371485/target-deconvolution-efforts-on-wnt-pathway-screen-reveal-dual-modulation-of-oxidative-phosphorylation-and-serca2
#20
Matias Casás-Selves, Andrew X Zhang, James E Dowling, Stefan Hallén, Aarti Kawatkar, Nicholas J Pace, Christopher R Denz, Timothy Pontz, Farzin Garahdaghi, Qing Cao, Alan Sabirsh, Kumar Thakur, Nichole O'Connell, Jun Hu, Iván Cornella-Taracido, Eranthie Weerapana, Michael Zinda, Robert A Goodnow, M Paola Castaldi
Wnt signaling is critical for development, cell proliferation and differentiation, and mutations in this pathway resulting in constitutive signaling have been implicated in various cancers. A pathway screen using a Wnt-dependent reporter identified a chemical series based on a 1,2,3-thiadiazole-5-carboxamide (TDZ) core with sub-micromolar potency. Herein we report a comprehensive mechanism-of-action deconvolution study toward identifying the efficacy target(s) and biological implication of this chemical series involving bottom-up quantitative chemoproteomics, cell biology, and biochemical methods...
June 21, 2017: ChemMedChem
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