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https://www.readbyqxmd.com/read/29779013/treatment-of-sec62-over-expressing-tumors-by-thapsigargin-and-trifluoperazine
#1
Christina Körbel, Maximilian Linxweiler, Florian Bochen, Silke Wemmert, Bernhard Schick, Markus Meyer, Hans Maurer, Michael D Menger, Richard Zimmermann, Markus Greiner
Treatment with analogues of the SERCA-inhibitor Thapsigargin is a promising new approach for a wide variety of cancer entities. However, our previous studies on various tumor cells suggested resistance of SEC62 over-expressing tumors to this treatment. Therefore, we proposed the novel concept that e.g. lung-, prostate-, and thyroid-cancer patients should be tested for SEC62 over-expression, and developed a novel therapeutic strategy for a combinatorial treatment of SEC62 over-expressing tumors. The latter was based on the observations that treatment of SEC62 over-expressing tumor cells with SEC62-targeting siRNAs showed less resistance to Thapsigargin as well as a reduction in migratory potential and that the siRNA effects can be mimicked by the Calmodulin antagonist Trifluoperazine...
May 19, 2018: Biomolecular Concepts
https://www.readbyqxmd.com/read/29764938/redistribution-of-serca-calcium-pump-conformers-during-intracellular-calcium-signaling
#2
Olga N Raguimova, Nikolai Smolin, Elisa Bovo, Siddharth Bhayani, Joseph M Autry, Aleksey V Zima, Seth L Robia
The conformational changes of a calcium transport A TPase were investigated with molecular dynamics (MD) simulations as well as fluorescence resonance energy transfer (FRET) measurements to determine the significance of a discrete structural element for regulation of the conformational dynamics of the transport cycle. Previous MD simulations indicated that a loop in the cytosolic domain of the SERCA calcium transporter facilitates an open-to-closed structural transition. To investigate the significance of this structural element, we performed additional MD simulations and new biophysical measurements of SERCA structure and function...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29752814/valproic-acid-inhibits-atp-triggered-ca-2-release-via-a-p38-dependent-mechanism-in-bend-3-endothelial-cells
#3
Iat-Lon Leong, Tien-Yao Tsai, Kar-Lok Wong, Lian-Ru Shiao, Ka-Shun Cheng, Paul Chan, Yuk-Man Leung
Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+ signaling is hitherto unreported. In this report we examined the effects of VA on agonist-triggered Ca2+ signaling in mouse cortical bEND.3 EC. While VA (100 μM) did not cause an acute inhibition of ATP-triggered Ca2+ signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca2+ release; however, such treatment did not affect Ca2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+ pump, suggesting there was no reduction in Ca2+ store size...
May 12, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29748131/underlying-mechanism-of-the-contractile-dysfunction-in-atrophied-ventricular-myocytes-from-a-murine-model-of-hypothyroidism
#4
Dolores Montalvo, Perla Pérez-Treviño, Katheryne Madrazo-Aguirre, Fabio A González-Mondellini, Hipólito O Miranda-Roblero, Diego Ramonfaur-Gracia, Mariana Jacobo-Antonio, Maritza Mayorga-Luna, Norma L Gómez-Víquez, Noemí García, Julio Altamirano
Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (Dmit ) and energy availability, is unclear...
February 5, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29748130/effects-of-the-iron-chelator-deferiprone-and-the-t-type-calcium-channel-blocker-efonidipine-on-cardiac-function-and-ca-2-regulation-in-iron-overloaded-thalassemic-mice
#5
Juthamas Khamseekaew, Sirinart Kumfu, Siripong Palee, Suwakon Wongjaikam, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
Although disturbance of cardiac Ca2+ regulation is involved in the pathophysiology of iron-overload cardiomyopathy, the obvious mechanisms involved in the dysregulation of iron-induced cardiac Ca2+ are unclear. Moreover, the roles of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac intracellular Ca2+ transients and Ca2+ regulatory proteins in thalassemic mice are still unknown. We tested the hypothesis that treatment with either deferiprone or efonidipine attenuated cardiac Ca2+ dysregulation and led to improved left ventricular (LV) function in iron-overloaded thalassemic mice...
February 6, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29723871/cd38-cadpr-serca-signaling-axis-determines-skeletal-muscle-contractile-force-in-response-to-%C3%AE-adrenergic-stimulation
#6
Dae-Ryoung Park, Tae-Sik Nam, Ye-Won Kim, Seo-Ho Lee, Uh-Hyun Kim
BACKGROUND/AIMS: Cyclic ADP-ribose (cADPR) is a Ca2+ -mobilization messenger that acts on ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum (SR) Ca2+ stores. Moreover, it has been proposed that cADPR serves an additional role in activating the sarcoendoplasmic reticulum Ca2+ -ATPase (SERCA) pump. The aim of this study was to determine the exact mechanism by which cADPR regulates SR Ca2+ stores in physiologically relevant systems. METHODS: We analyzed Ca2+ signals as well as the production of Ca2+ mobilizing messengers in the skeletal muscle cells of mice subjected to intensive exercise or in the SR fractions from skeletal muscle cells after β-adrenergic receptor (β-AR) stimulation...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29723269/17%C3%AE-estradiol-and-or-estrogen-receptor-alpha-signaling-blocks-protein-phosphatase-1-mediated-iso-induced-cardiac-hypertrophy
#7
Hsin-Yuan Fang, Meng-Yu Hung, Yueh-Min Lin, Sudhir Pandey, Chia-Chien Chang, Kuan-Ho Lin, Chia-Yao Shen, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
Earlier studies have shown that estrogen possess protective function against the development of pathological cardiac hypertrophy. However, the molecular mechanisms of estrogens (E2) protective effect are poorly understood. Additionally, abnormal activation of β-adrenergic signaling have been implicated in the development of pathological cardiac remodeling. However, the role of serine/threonine protein phosphatase 1 (PP1) in pathological cardiac remodeling under the influence of β-adrenergic signaling have been sparsely investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29715473/stabilization-of-ca-2-signaling-in-cardiac-muscle-by-stimulation-of-serca
#8
Miguel Fernandez-Tenorio, Ernst Niggli
AIMS: In cardiac muscle, phosphorylation of the RyRs is proposed to increase their Ca2+ sensitivity. This mechanism could be arrhythmogenic via facilitation of spontaneous Ca2+ waves. Surprisingly, the level of Ca2+ inside the SR needed to initiate such waves has been reported to increase upon β-adrenergic stimulation, an observation which cannot be easily reconciled with elevated Ca2+ sensitivity of the RyRs. We tested the hypothesis that this change of Ca2+ wave threshold could occur indirectly, subsequent to SERCA stimulation...
April 30, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29699580/genetic-deletion-of-muscle-rank-or-selective-inhibition-of-rankl-is-not-as-effective-as-full-length-opg-fc-in-mitigating-muscular-dystrophy
#9
Sébastien S Dufresne, Antoine Boulanger-Piette, Sabrina Bossé, Anteneh Argaw, Dounia Hamoudi, Laetitia Marcadet, Daniel Gamu, Val A Fajardo, Hideo Yagita, Josef M Penninger, A Russell Tupling, Jérôme Frenette
Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that regulates synchronously bone and skeletal muscle physiopathology is still elusive. Receptor-activator of nuclear factor κB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG) are the key regulators of osteoclast differentiation and bone remodelling. We thus hypothesized that RANK/RANKL/OPG, which is a key pathway for bone regulation, is involved in Duchenne muscular dystrophy (DMD) physiopathology...
April 24, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29696147/drug-interactions-with-the-ca-2-atpase-from-sarco-endo-plasmic-reticulum-serca
#10
REVIEW
Francesco Tadini-Buoninsegni, Serena Smeazzetto, Roberta Gualdani, Maria Rosa Moncelli
The sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) is an intracellular membrane transporter that utilizes the free energy provided by ATP hydrolysis for active transport of Ca2+ ions from the cytoplasm to the lumen of sarco(endo)plasmic reticulum. SERCA plays a fundamental role for cell calcium homeostasis and signaling in muscle cells and also in cells of other tissues. Because of its prominent role in many physiological processes, SERCA dysfunction is associated to diseases displaying various degrees of severity...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29684447/type-3-iodothyronine-deiodinase-is-expressed-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#11
Kumiko Nishimura, Masafumi Takeda, Jun K Yamashita, Ichiro Shiojima, Nagaoki Toyoda
AIMS: Type 3 iodothyronine deiodinase (D3), which converts thyroxine (T4 ) and 3,5,3'-triiodothyronine (T3 ) to 3,3',5'-triiodothyronine (rT3 ) and 3,3'-diiodothyronine (T2 ), respectively, inactivates thyroid hormones. We investigated the expression and regulation of D3 in human cardiomyocytes which were differentiated from human induced pluripotent stem cells (hiPSCs). MAIN METHODS: We characterized D3 activity using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis...
April 20, 2018: Life Sciences
https://www.readbyqxmd.com/read/29675630/saikosaponin-d-inhibits-proliferation-by-up-regulating-autophagy-via-the-camkk%C3%AE-ampk-mtor-pathway-in-adpkd-cells
#12
Weiwei Shi, Dechao Xu, Junhui Gu, Cheng Xue, Bo Yang, Lili Fu, Shuwei Song, Dongmei Liu, Wei Zhou, Jiayi Lv, Ke Sun, Meihan Chen, Changlin Mei
Autosomal dominant polycystic kidney disease (ADPKD) is a common heritable human disease. Recently, the role of repressed autophagy in ADPKD has drawn increasing attention. Here, we investigate the mechanism underlying the effect of Saikosaponin-d (SSd), a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA) inhibitor. We show that SSd suppresses proliferation in ADPKD cells by up-regulating autophagy. We found that treatment with SSd results in the accumulation of intracellular calcium, which in turn activates the CaMKKβ-AMPK signalling cascade, inhibits mTOR signalling and induces autophagy...
April 19, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29662923/effects-of-electrical-stimulation-on-skeletal-muscle-of-old-sedentary-people
#13
Simone Mosole, Sandra Zampieri, Sandra Furlan, Ugo Carraro, Stefan Löefler, Helmut Kern, Pompeo Volpe, Alessandra Nori
Physical activity plays an important role in preventing muscle atrophy and chronic diseases in adults and in the elderly. Calcium (Ca2+ ) cycling and activation of specific molecular pathways are essential in contraction-induced muscle adaptation. This study attains human muscle sections and total homogenates prepared from biopsies obtained before (control) and after 9 weeks of training by electrical stimulation (ES) on a group of volunteers. The aim of the study was to investigate about the molecular mechanisms that support functional muscle improvement by ES...
January 2018: Gerontology & Geriatric Medicine
https://www.readbyqxmd.com/read/29653363/trapidil-improves-hemodynamic-echocardiographic-and-redox-state-parameters-of-right-ventricle-in-monocrotaline-induced-pulmonary-arterial-hypertension-model
#14
Patrick Türck, Denise Santos Lacerda, Cristina Campos Carraro, Bruna Gazzi de Lima-Seolin, Rayane Brinck Teixeira, Jéssica Hellen Poletto Bonetto, Rafael Colombo, Paulo Cavalheiro Schenkel, Adriane Belló-Klein, Alex Sander da Rosa Araujo
BACKGROUND: Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions. HYPOTHESIS: Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH. METHODS AND RESULTS: Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil...
April 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29607318/calcitriol-prevents-cardiovascular-repercussions-in-puromycin-aminonucleoside-induced-nephrotic-syndrome
#15
Fernandes-Cerqueira Cátia, Quelhas-Santos Janete, Sampaio-Maia Benedita, Simões-Silva Liliana, Soares-Silva Isabel, Roncon-Albuquerque Roberto, Pestana Manuel
Puromycin aminonucleoside-induced nephrotic syndrome (PAN-NS) is characterized by cardiac remodeling and increased local inflammatory activity. Patients with NS and animal models of NS have vitamin D3 deficiency. The aim of the present study was to evaluate the influence of calcitriol on cardiac remodeling and local inflammatory state in PAN-NS rat model. Male Sprague-Dawley rats were injected with PAN or vehicle on day 0. PAN and control rats were divided into two subgroups for the administration of calcitriol (PAN-D and Ct-D groups) or the vehicle (PAN-V and Ct-V groups) during 21 days...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29604965/computational-modeling-of-amylin-induced-calcium-dysregulation-in-rat-ventricular-cardiomyocytes
#16
Bradley D Stewart, Caitlin E Scott, Thomas P McCoy, Guo Yin, Florin Despa, Sanda Despa, Peter M Kekenes-Huskey
Hyperamylinemia is a condition that accompanies obesity and precedes type II diabetes, and it is characterized by above-normal blood levels of amylin, the pancreas-derived peptide. Human amylin oligomerizes easily and can deposit in the pancreas [1], brain [2], and heart [3], where they have been associated with calcium dysregulation. In the heart, accumulating evidence suggests that human amylin oligomers form moderately cation-selective [4,5] channels that embed in the cell sarcolemma (SL). The oligomers increase membrane conductance in a concentration-dependent manner [5], which is correlated with elevated cytosolic Ca2+ ...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29604267/serca-plays-a-crucial-role-in-the-toxicity-of-a-betulinic-acid-derivative-with-potential-antimalarial-activity
#17
Denise Diedrich, Andreia C Wildner, Thayse F Silveira, Gloria N S Silva, Francine Dos Santos, Vanessa Petry do Canto, Grace Gosmann, Ana Maria Bergold, Aline R Zimmer, Paulo A Netz, Simone C B Gnoatto
Malaria is one of the most significant infectious diseases that affect poor populations in tropical areas throughout the world. Plants have been shown to be a good source for the development of new antimalarial chemotherapeutic agents, as shown for the discovery of quinine and artemisinin derivatives. Our research group has been working with semisynthetic triterpene derivatives that show potential antimalarial activity toward different strains of Plasmodium falciparum by specifically modulating calcium pathways in the parasite...
March 28, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29602679/a-new-target-for-alzheimer-s-disease-a-small-molecule-serca-activator-is-neuroprotective-in-vitro-and-improves-memory-and-cognition-in-app-ps1-mice
#18
Katherine Krajnak, Russell Dahl
Amongst the cellular cacophony of altered signals in Alzheimer's disease (AD), disrupted Ca2+ homeostasis and consequential endoplasmic reticulum (ER) stress signals have been recognized as key determinants of neuron fate. This altered Ca2+ state is accompanied by a failing sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) pump, which has been recognized as a causal feature of the underlying disease state. Repair of the Ca2+ dyshomeostasis represents a putative drug target via alleviation of ER stress and rescue of injured neurons, effectively modifying the AD state...
March 21, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29601947/imaging-the-secretory-compartments-involved-in-the-intracellular-traffic-of-chs-4-a-class-iv-chitin-synthase-in-neurospora-crassa
#19
Adriana M Rico-Ramírez, Robert W Roberson, Meritxell Riquelme
In Neurospora crassa hyphae the localization of all seven chitin synthases (CHSs) at the Spitzenkörper (Spk) and at developing septa has been well analyzed. Hitherto, the mechanisms of CHSs traffic and sorting from synthesis to delivery sites remain largely unexplored. In Saccharomyces cerevisiae exit of Chs3p from the endoplasmic reticulum (ER) requires chaperone Chs7p. Here, we analyzed the role of CSE-7, N. crassa Chs7p orthologue in the biogenesis of CHS-4 (orthologue of Chs3p). In a N. crassa Δcse-7 mutant, CHS-4-GFP no longer accumulated at the Spk and septa...
March 27, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29601906/melatonin-therapy-for-diabetic-cardiomyopathy-a-mechanism-involving-syk-mitochondrial-complex-i-serca-pathway
#20
Hao Zhou, Yan Yue, Jin Wang, Qiang Ma, Yundai Chen
Melatonin and its metabolites have been demonstrated to modulate the glucose, dyslipidemia and other metabolic disorders. This study aimed to explore a novel mechanism responsible for diabetic cardiomyopathy development, and also validated whether melatonin played a protective role in repairing damaged heart in the diabetes setting. Our data demonstrated that spleen tyrosine kinase (Syk) was activated by chronic high-glucose stimulus and contributed to the development of diabetic cardiomyopathy. However, genetic ablation of Syk or supplementation of melatonin to inhibit Syk activation improved diabetic myocardial function, reduced cardiac fibrosis and preserved cardiomyocytes viability...
July 2018: Cellular Signalling
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