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https://www.readbyqxmd.com/read/28094886/the-parathyroid-hormone-family-member-tip39-interacts-with-sarco-endoplasmic-reticulum-ca-2-atpase-activity-by-influencing-calcium-homeostasis
#1
Emi Sato, Michael R Williams, James A Sanford, George L Sen, Takekuni Nakama, Shinichi Imafuku, Richard L Gallo
Darier disease (DD) is a genetic skin disease that is associated with mutations in the ATP2A2 gene encoding the type 2 sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA2). Mutations of this gene result in alterations of calcium homeostasis, abnormal epidermal adhesion and dyskeratosis. Silencing of ATP2A2 in monolayer cell culture of keratinocytes reduces desmoplakin expression at the borders of cells and impacts cell adhesion. Here, we report establishment of a three-dimensional (3D) epidermal model of DD, and use this model to evaluate peptide therapy with tuberoinfundibular peptide of 39 residues (TIP39) to normalize calcium transport...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28008204/novel-and-recurrent-atp2a2-mutations-in-japanese-patients-with-darier-s-disease
#2
Kana Noda, Takuya Takeichi, Yusuke Okuno, Hiromichi Takama, Shunsuke Miura, Shinji Kagami, Haruko Hino, Yuki Nakamura, Yumi Fujio, Izumi Konohana, Ayako Otani, Hideki Mukai, Kazumitsu Sugiura, Masashi Akiyama
Darier's disease (DD, keratosis follicularis: OMIM#124200) is an autosomal dominant skin disorder characterized by multiple dark brown keratotic plaques and warty papules covered by thick crusts. Most cases of DD are caused by mutations in ATP2A2, which is expressed in both the skin and the brain. ATP2A2 encodes the cardiac muscle SERCA2a protein and the ubiquitously expressed SERCA2b. SERCA2 plays an important role as a calcium pump. It is thought that a mutation in ATP2A2 causes dyskeratosis and abnormality of cell-cell adhesion...
December 2016: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/27931779/complement-and-sepsis-induced-heart-dysfunction
#3
Fatemeh Fattahi, Peter A Ward
It is well known that cardiac dysfunction develops during sepsis in both humans and in rodents (rats, mice). These defects appear to be reversible, since after "recovery" from sepsis, cardiac dysfunction disappears and the heart returns to its function that was present before the onset of sepsis. Our studies, using in vivo and in vitro models, have demonstrated that C5a and its receptors (C5aR1 and C5aR2) play key roles in cardiac dysfunction developing during sepsis. Use of a neutralizing antibody to C5a largely attenuates cardiac dysfunction and other adverse events developing during sepsis...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27872214/effects-of-prolonged-anoxia-on-electrical-activity-of-the-heart-in-crucian-carp-carassius-carassius
#4
Elisa Tikkanen, Jaakko Haverinen, Stuart Egginton, Minna Hassinen, Matti Vornanen
The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant Crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 to 4.1±0.29 bpm (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored...
November 21, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27856713/effect-of-increased-and-maintained-frequency-of-speed-endurance-training-on-performance-and-muscle-adaptations-in-runners
#5
Casper Skovgaard, Nicki Winfield Almquist, Jens Bangsbo
: The aim of the study was, in runners accustomed to speed endurance training (SET), to examine the effect of increased and maintained frequency of SET on performance and muscular adaptations. After familiarization (FAM) to SET, 18 male (n = 14) and female (n = 4) runners (V̇o2max: 57.3 ± 3.4 ml/min; means ± SD) completed 20 sessions of maintained low-frequency (LF; every fourth day; n = 7) or high-frequency (HF; every second day; n = 11) SET. Before FAM as well as before and after an intervention period (INT), subjects completed a series of running tests and a biopsy from m...
January 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27856611/loss-of-akap150-promotes-pathological-remodelling-and-heart-failure-propensity-by-disrupting-calcium-cycling-and-contractile-reserve
#6
Lei Li, Jing Li, Benjamin M Drum, Yi Chen, Haifeng Yin, Xiaoyun Guo, Stephen W Luckey, Merle L Gilbert, G Stanley McKnight, John D Scott, L Fernando Santana, Qinghang Liu
AIMS: Impaired Ca(2 + )cycling and myocyte contractility are a hallmark of heart failure triggered by pathological stress such as hemodynamic overload. The A-Kinase anchoring protein AKAP150 has been shown to coordinate key aspects of adrenergic regulation of Ca(2+ )cycling and excitation-contraction in cardiomyocytes. However, the role of the AKAP150 signalling complexes in the pathogenesis of heart failure has not been investigated. METHODS AND RESULTS: Here we examined how AKAP150 signalling complexes impact Ca(2+ )cycling, myocyte contractility, and heart failure susceptibility following pathological stress...
November 17, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27853260/the-synthetic-antimicrobial-peptide-19-2-5-attenuates-septic-cardiomyopathy-and-prevents-down-regulation-of-serca2-in-polymicrobial-sepsis
#7
Lukas Martin, Klemens Horst, Fausto Chiazza, Silvia Oggero, Massimo Collino, Klaus Brandenburg, Frank Hildebrand, Gernot Marx, Christoph Thiemermann, Tobias Schuerholz
An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca(2+)-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves outcome in sepsis. Thus, we investigated whether the administration of the synthetic antimicrobial peptide Pep2.5 may attenuate the cardiac dysfunction in murine polymicrobial sepsis through regulating SERCA2 expression...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27737958/mechanical-stress-conditioning-and-electrical-stimulation-promote-contractility-and-force-maturation-of-induced-pluripotent-stem-cell-derived-human-cardiac-tissue
#8
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUND: Tissue engineering enables the generation of functional human cardiac tissue with cells derived in vitro in combination with biocompatible materials. Human-induced pluripotent stem cell-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electric pacing on the maturation of human-induced pluripotent stem cell-derived cardiac tissues...
November 15, 2016: Circulation
https://www.readbyqxmd.com/read/27737323/thyroxine-increases-serca2-and-ryr2-gene-expression-in-heart-failure-rats-with-euthyroid-sick-syndrome
#9
Fábio V G Campanha, Denise Perone, Dijon H S de Campos, Renata de A M Luvizotto, Maria T De Síbio, Miriane de Oliveira, Regiane M C Olimpio, Fernanda C F Moretto, Carlos R Padovani, Gláucia M F S Mazeto, Antonio C Cicogna, Célia R Nogueira
Objective: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups...
November 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27721754/exacerbation-of-darier-disease-under-interferon-%C3%AE-2a-therapy-with-clinical-signs-of-lichen-nitidus
#10
Ioannis Karagiannidis, Martina Brunner, Christos C Zouboulis
Darier disease/dyskeratosis follicularis is a genodermatosis characterized by brown, oily keratotic papules and plaques in the seborrheic areas of the face and chest. Responsible for the disease are mutations in the ATP2A2 gene, encoding SERCA2, a calcium pump of the sarco-/endoplasmic reticulum. Mechanical trauma, heat, humidity, ultraviolet B radiation, oral corticosteroids and lithium are known trigger factors of the disorder. We report on a 48-year-old German woman with a flare-up of Darier disease under interferon-α-2a (IFNα-2a) therapy with clinical signs of lichen nitidus...
May 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/27688314/genotype-dependent-and-independent-calcium-signaling-dysregulation-in-human-hypertrophic-cardiomyopathy
#11
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27545043/mir-208b-upregulation-interferes-with-calcium-handling-in-hl-1-atrial-myocytes-implications-in-human-chronic-atrial-fibrillation
#12
Susana Cañón, Ricardo Caballero, Adela Herraiz-Martínez, Marta Pérez-Hernández, Begoña López, Felipe Atienza, José Jalife, Leif Hove-Madsen, Eva Delpón, Antonio Bernad
microRNAs (miR) have considerable potential as therapeutic tools in cardiac diseases. Alterations in atrial miR are involved in the development of atrial fibrillation (AF), but the molecular mechanism underlying their contribution to atrial remodeling in chronic atrial fibrillation (CAF) is only partially understood. Here we used miR array to analyze the miR profile of atrial biopsies from sinus rhythm (SR) and CAF patients. qRT-PCR identified a distinctive CAF-miR signature and described conserved miR-208b upregulation in human and ovine AF atrial tissue...
August 18, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27538371/sarcoplasmic-reticulum-ca-2-atpase-2-serca2-reduces-the-migratory-capacity-of-ccl21-treated-monocyte-derived-dendritic-cells
#13
Cheol Yi Hong, Hyun-Ju Lee, Nu-Ri Choi, Sung-Hoon Jung, Manh-Cuong Vo, My Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins...
2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27529477/nitric-oxide-synthase-1-modulates-basal-and-%C3%AE-adrenergic-stimulated-contractility-by-rapid-and-reversible-redox-dependent-s-nitrosylation-of-the-heart
#14
Alejandra Z Vielma, Luisa León, Ignacio C Fernández, Daniel R González, Mauricio P Boric
S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC...
2016: PloS One
https://www.readbyqxmd.com/read/27489309/serca2-deficiency-impairs-pancreatic-%C3%AE-cell-function-in-response-to-diet-induced-obesity
#15
Xin Tong, Tatsuyoshi Kono, Emily K Anderson-Baucum, Wataru Yamamoto, Patrick Gilon, Djamel Lebeche, Richard N Day, Gary E Shull, Carmella Evans-Molina
The sarcoendoplasmic reticulum (ER) Ca(2+) ATPase 2 (SERCA2) pump is a P-type ATPase tasked with the maintenance of ER Ca(2+) stores. Whereas β-cell SERCA2 expression is reduced in diabetes, the role of SERCA2 in the regulation of whole-body glucose homeostasis has remained uncharacterized. To this end, SERCA2 heterozygous mice (S2HET) were challenged with a high-fat diet (HFD) containing 45% of kilocalories from fat. After 16 weeks of the HFD, S2HET mice were hyperglycemic and glucose intolerant, but adiposity and insulin sensitivity were not different between HFD-fed S2HET mice and HFD-fed wild-type controls...
October 2016: Diabetes
https://www.readbyqxmd.com/read/27487922/malonate-in-the-nucleotide-binding-site-traps-human-akap18%C3%AE-%C3%AE-in-a-novel-conformational-state
#16
Kaare Bjerregaard-Andersen, Ellen Østensen, John D Scott, Kjetil Taskén, Jens Preben Morth
A-kinase anchoring proteins (AKAPs) are a family of proteins that provide spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the myocardium, PKA and AKAP18γ/δ are found in complex with sarcoendoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular complex provides a means by which anchored PKA can dynamically regulate cytoplasmic Ca(2+) release and re-uptake. For this reason, AKAP18γ/δ presents an interesting drug target with therapeutic potential in cardiovascular disease...
August 2016: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/27313537/ca-2-clock-dependent-pacemaking-in-the-sinus-node-is-impaired-in-mice-with-a-cardiac-specific-reduction-in-serca2-abundance
#17
Sunil Jit R J Logantha, Mathis K Stokke, Andrew J Atkinson, Sanjay R Kharche, Sajida Parveen, Yawer Saeed, Ivar Sjaastad, Ole M Sejersted, Halina Dobrzynski
BACKGROUND: The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) pump is an important component of the Ca(2+)-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. METHODS AND RESULTS: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P < 0...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27240156/relaxin-2-improves-diastolic-function-of-pressure-overloaded-rats-via-phospholamban-by-activating-akt
#18
Xin-Xin Shuai, Yi-di Meng, Yong-Xin Lu, Guan-Hua Su, Xiao-Fang Tao, Jun Han, Su-Dan Xu, Ping Luo
BACKGROUND: Relaxin is a peptide hormone which has been demonstrated to be safe and has a therapeutic effect on acute heart failure in clinic trials. However, its effect on diastolic function is still unknown. The aims of the study were to determine whether relaxin could improve the diastolic function in pressure-overloaded rat model and to analyze potential mechanisms. METHODS AND RESULTS: In the present study, a pressure-overloaded rat model induced by transaortic constriction (TAC) was established...
September 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27239807/adenine-induced-chronic-renal-failure-in-rats-decreases-aortic-relaxation-rate-and-alters-expression-of-proteins-involved-in-vascular-smooth-muscle-calcium-handling
#19
L Nguy, E Shubbar, M Jernås, I Nookaew, J Lundgren, B Olsson, H Nilsson, G Guron
AIM: Rats with adenine-induced chronic renal failure (A-CRF) develop a reduced rate of relaxation of the thoracic aorta. The aim of this study was to elucidate the mechanisms underlying this abnormality. METHODS: Male Sprague Dawley rats received either chow containing adenine or were pair-fed with normal chow (controls). After 8-14 weeks, arterial function was analysed ex vivo using wire myography and the expression of proteins involved in vascular smooth muscle excitation-contraction coupling in the thoracic aorta was analysed...
December 2016: Acta Physiologica
https://www.readbyqxmd.com/read/27179211/long-term-administration-of-ranolazine-attenuates-diastolic-dysfunction-and-adverse-myocardial-remodeling-in-a-model-of-heart-failure-with-preserved-ejection-fraction
#20
Antonella De Angelis, Donato Cappetta, Elena Piegari, Barbara Rinaldi, Loreta Pia Ciuffreda, Grazia Esposito, Fiorella Angelica Valeria Ferraiolo, Alessia Rivellino, Rosa Russo, Maria Donniacuo, Francesco Rossi, Konrad Urbanek, Liberato Berrino
BACKGROUND: To investigate the effects of chronic administration of ranolazine (RAN) on experimental model of heart failure with preserved ejection fraction. METHODS: Seven-weeks old Dahl salt-sensitive rats were fed a high salt diet for 5weeks to induce hypertension. Afterwards, rats continued with a high salt diet and were administered either with vehicle or RAN (20mg/kg/die, ip) for the following 8weeks. Control rats were maintained on a low salt diet. RESULTS: While systolic parameters were not altered, diastolic parameters were changed in high salt animals...
August 15, 2016: International Journal of Cardiology
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