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https://www.readbyqxmd.com/read/27922120/regulation-of-human-cardiac-potassium-channels-by-full-length-kcne3-and-kcne4
#1
Geoffrey W Abbott
Voltage-gated potassium (Kv) channels comprise pore-forming α subunits and a multiplicity of regulatory proteins, including the cardiac-expressed and cardiac arrhythmia-linked transmembrane KCNE subunits. After recently uncovering novel, N-terminally extended (L) KCNE3 and KCNE4 isoforms and detecting their transcripts in human atrium, reported here are their functional effects on human cardiac Kv channel α subunits expressed in Xenopus laevis oocytes. As previously reported for short isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919547/granuloma-formation-in-a-patient-with-gne-myopathy-a-case-report
#2
Keiko Nakamura, Tsuyoshi Hamaguchi, Kenji Sakai, Daisuke Noto, Kenjiro Ono, Yukiko Hayashi, Ichizo Nishino, Masahito Yamada
We report a patient with GNE myopathy with a homozygous mutation (c.1505-4G>A) in GNE gene. The patient recognized progressive weakness of extremities at age 60. Neurological examination at age 65 revealed severe weakness and atrophy in the tibialis anterior muscles and distal predominant moderate weakness in the extremities. Muscle biopsy performed at age 65 showed myopathic changes with rimmed vacuoles, and the noteworthy finding was non-caseating epithelioid cell granuloma formation surrounded by numerous inflammatory cells...
November 18, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27916793/histone-h3-methyltransferase-suv39h1-prevents-myogenic-terminal-differentiation-by-repressing-mef2-activity-in-muscle-cells
#3
Wei Jin, Yangyang Shang, Jian Peng, Siwen Jiang
The myogenic regulatory factors (MRFs) and myocyte enhancer factor 2 (MEF2) transcription factors have been extensively studied as key transcription factors that regulate myogenic gene expression. However, few reports on the molecular mechanism that modulates chromatin remodeling during skeletal muscle differentiation are available. We reported here that the expression of the H3-K9 methyltransferase Suv39h1 was decreased during myoblast differentiation. Ectopic expression of Suv39h1 could inhibit myoblast differentiation, increasing H3-K9 methylation levels, whereas knockdown of Suv39h1 stimulated myoblast differentiation...
November 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916606/fbx8-is-a-metastasis-suppressor-downstream-of-mir-223-and-targeting-mtor-for-degradation-in-colorectal-cancer
#4
F F Wang, X J Zhang, Y R Yan, X H Zhu, J Yu, Y Ding, J L Hu, W J Zhou, Z C Zeng, W T Liao, Y Q Ding, L Liang
F-box proteins are critical components of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases and involved in the ubiquitin-dependent proteolytic pathway. Dysregulation of F-box protein-mediated proteolysis often leads to human malignancies. F-box only protein 8 (FBX8), a novel component of F-box proteins, is down-regulated in several tumors and closely correlates with tumor progression. However, little is known about its function, regulatory mechanisms and substrates in the progression of colorectal cancer (CRC)...
December 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27915452/chronic-enalapril-treatment-increases-transient-outward-potassium-current-in-cardiomyocytes-isolated-from-right-ventricle-of-spontaneously-hypertensive-rats
#5
Luiz Fernando Rodrigues Junior, Ana Carolina de Azevedo Carvalho, Enildo Broetto Pimentel, José Geraldo Mill, José Hamilton Matheus Nascimento
It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR)...
December 3, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27915160/histone-deacetylase-9-plays-a-role-in-the-antifibrogenic-effect-of-astaxanthin-in-hepatic-stellate-cells
#6
Yue Yang, Minkyung Bae, Young-Ki Park, Yoojin Lee, Tho X Pham, Swetha Rudraiah, José Manautou, Sung I Koo, Ji-Young Lee
Activation of hepatic stellate cells (HSCs) is critical for liver fibrosis development. Previously, we showed that astaxanthin (ASTX), a xanthophyll carotenoid, has antifibrogenic effects in LX-2 cells, a human HSC cell line. We sought to determine the effect of ASTX on HSC activation, and to identify molecular mediators that are critically involved in the processes. ASTX prevented the activation of mouse primary HSCs, as evidenced by attenuated induction of procollagen type I α1. In human primary HSCs, ASTX also inhibited transforming growth factor β1 (TGFβ1)-induced fibrogenic gene expression...
November 12, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27915058/larger-rate-dependence-of-late-sodium-current-in-cardiac-purkinje-cells-a-potential-link-to-arrhythmogenesis
#7
Wei Li, Ying Yu, Jian-Wen Hou, Zhi-Wen Zhou, Kai Guo, Peng-Pai Zhang, Zhi-Quan Wang, Jian-Hua Yan, Jian Sun, Qing Zhou, Yue-Peng Wang, Yi-Gang Li
BACKGROUND: Purkinje cells (PCs) have steeper rate-dependence of repolarization and are more susceptible to arrhythmic activity than ventricular myocytes (VMs). Late sodium current (INaL) is rate-dependent and contributes to rate-dependence of repolarization. OBJECTIVE: This study sought to test our hypothesis that PCs have larger rate-dependence of INaL, contributing to their steeper rate-dependence of repolarization and higher susceptibility to arrhythmic activity than VMs...
November 30, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27915047/physical-and-functional-interaction-of-snapin-with-cav1-3-calcium-channel-impacts-channel-protein-trafficking-in-atrial-myocytes
#8
Xiao-Li Sun, Ju-Fang Yuan, Tao Jin, Xiao-Qing Cheng, Qiang Wang, Jia Guo, Wei Zhang, Yin Zhang, Ling Lu, Zhao Zhang
The L-type Ca(2+) channel (LTCC) Cav1.3 playsa critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both theheterologous expression system and mouse atrial myocytes...
November 30, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27910057/molecular-cardiac-surgery-with-recirculating-delivery-mcard-procedure-and-vector-transfer
#9
Michael G Katz, Anthony S Fargnoli, Andrew P Kendle, Charles R Bridges
Despite progress in clinical treatment, cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Therefore, novel therapeutic approaches are needed, targeting the underlying molecular mechanisms of disease with improved outcomes for patients. Gene therapy is one of the most promising fields for the development of new treatments for the advanced stages of cardiovascular diseases. The establishment of clinically relevant methods of gene transfer remains one of the principal limitations on the effectiveness of gene therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27908250/hypoglycemia-and-cardiac-arrhythmia-mechanisms-evidence-base-and-current-recommendations
#10
Sitara Gulrukh Khan, Mohammed Shahriar Huda
BACKGROUND: With the use of intensive insulin therapy and insulin secretagogues to optimize glycemic control in diabetes, hypoglycemia continues to present a clinical challenge. Hypoglycemia has been implicated in nocturnal sudden death in type 1 diabetes, and the mechanism underlying this is postulated to be cardiac arrhythmia. OBJECTIVE: This article reviews the evidence surrounding hypoglycemia and cardiac arrhythmia. METHODS: A structured search of the Pubmed bibliographic database was undertaken, and relevant peer-reviewed articles on the topic were included in the review...
December 1, 2016: Current Diabetes Reviews
https://www.readbyqxmd.com/read/27907007/exploring-regulatory-mechanisms-of-atrial-myocyte-hypertrophy-of-mitral-regurgitation-through-gene-expression-profiling-analysis-role-of-nfat-in-cardiac-hypertrophy
#11
Tzu-Hao Chang, Mien-Cheng Chen, Jen-Ping Chang, Hsien-Da Huang, Wan-Chun Ho, Yu-Sheng Lin, Kuo-Li Pan, Yao-Kuang Huang, Wen-Hao Liu, Chia-Chen Wu
BACKGROUND: Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. METHODS AND RESULTS: This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC...
2016: PloS One
https://www.readbyqxmd.com/read/27906129/the-evolutionary-origin-of-bilaterian-smooth-and-striated-myocytes
#12
Thibaut Brunet, Antje Hl Fischer, Patrick Rh Steinmetz, Antonella Lauri, Paola Bertucci, Detlev Arendt
The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed, and nervous control...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27904701/sirt6-suppresses-mitochondrial-defects-and-cell-death-via-the-nf-%C3%AE%C2%BAb-pathway-in-myocardial-hypoxia-reoxygenation-induced-injury
#13
Ming-Yue Cheng, You-Wei Cheng, Jun Yan, Xiao-Qin Hu, Hui Zhang, Zhi-Rong Wang, Qin Yin, Wei Cheng
The present study explored changes of the SIRT6/NF-κB pathway in myocardial hypoxia/reoxygenation induced injury and the effects on mitochondrial damage and myocardial damage by regulating SIRT6. SIRT6 expression decreased and NF-κB expression increased in H9c2 cells during hypoxic injury. Cell death and mitochondrial defects paralleled mPTP opening, and a decrease in ΔΨm occurred in hypoxic myocytes compared with normoxic control cells in annexin V and propidium iodide staining and TUNEL results. These effects were suppressed in cells overexpressing SIRT6, but reemerged in cells expressing the SIRT6 mutant...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903587/changes-in-mitochondrial-morphology-and-organisation-can-enhance-energy-supply-from-mitochondrial-oxidative-phosphorylation-in-diabetic-cardiomyopathy
#14
Jan Jarosz, Shouryadipta Ghosh, Lea M D Delbridge, Amorita Volschenk, Anthony Jr Hickey, Edmund J Crampin, Eric Hanssen, Vijay Rajagopal
Diabetic cardiomyopathy is accompanied by metabolic and ultrastructural alterations, but the impact of the structural changes on metabolism itself is yet to be determined. Morphometric analysis of mitochondrial shape and spatial organisation within transverse sections of cardiomyocytes from control and streptozotocin induced type I diabetic Sprague-Dawley rats revealed that mitochondria are 20% smaller in size while their spatial density increases by 53% in diabetic cells relative to control myocytes. Diabetic cells formed larger clusters of mitochondria (60% more mitochondria per cluster) and the effective surface to volume ratio of these clusters increased by 22...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903582/threshold-levels-of-extracellular-l-arginine-that-trigger-nos-mediated-ros-rns-production-in-cardiac-ventricular-myocytes
#15
Jayalakshmi Ramachandran, R Daniel Peluffo
L-arginine (L-Arg) is the substrate for nitric oxide synthase (NOS) to produce nitric oxide (NO), a signaling molecule that is key in cardiovascular physiology and pathology. In cardiac myocytes, L-Arg is incorporated from the circulation through the functioning of system-y(+) cationic amino acid transporters. Depletion of L-Arg leads to NOS uncoupling, with O2 rather than L-Arg as terminal electron acceptor, resulting in superoxide formation. The reactive oxygen species (ROS) superoxide (O2•(-)), combined with NO, may lead to the production of the reactive nitrogen species (RNS) peroxynitrite (ONOO-), which is recognized as a major contributor to myocardial depression...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903458/cardiac-arrest-among-patients-with-infections-causes-clinical-practice-and-research-implications
#16
REVIEW
Davide Leoni, Jordi Rello
The incidence of sepsis is increasing, and the condition is now the leading cause of death in general intensive care units (ICUs). Our review failed to identify studies of the causes of cardiac arrest among infected patients, even though non-cardiac causes represent 15% of out-of-hospital cardiac arrests and though one-third of events have positive blood cultures. Sudden cardiac arrest is the result of local damage to the heart and of the impact of systemic and pulmonary conditions on cardiac performance, and its danger is underestimated...
November 26, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27903291/erratum-to-high-expression-of-myocyte-enhancer-factor-2c-mef2c-is-associated-with-adverse-risk-features-and-poor-outcome-in-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#17
George S Laszlo, Todd A Alonzo, Chelsea J Gudgeon, Kimberly H Harrington, Alex Kentsis, Robert B Gerbing, Yi-Cheng Wang, Rhonda E Ries, Susana C Raimondi, Betsy A Hirsch, Alan S Gamis, Soheil Meshinchi, Roland B Walter
No abstract text is available yet for this article.
November 30, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27902841/dynamical-effects-of-calcium-sensitive-potassium-currents-on-voltage-and-calcium-alternans
#18
Matthew Kennedy, Donald M Bers, Nipavan Chiamvimonvat, Daisuke Sato
Cardiac alternans is a precursor to life-threatening arrhythmias. Alternans can be caused by instability of the membrane voltage (Vm ), instability of the intracellular Ca (Cai ) cycling, or both. Vm dynamics and Cai dynamics are coupled via Ca-sensitive currents. In cardiac myocytes, there are several Ca-sensitive potassium (K) currents such as the slowly activating delayed rectifier current (IKs ) and the small conductance Ca-activated potassium (SK) current (ISK ). However, the role of these currents in the development of arrhythmias is not well understood...
November 30, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27902477/astragalus-polysaccharide-restores-autophagic-flux-and-improves-cardiomyocyte-function-in-doxorubicin-induced-cardiotoxicity
#19
Yuan Cao, Tao Shen, Xiuqing Huang, Yajun Lin, Beidong Chen, Jing Pang, Guoping Li, Que Wang, Sylvia Zohrabian, Chao Duan, Yang Ruan, Yong Man, Shu Wang, Jian Li
Doxorubicin (adriamycin), an anthracycline antibiotic, is commonly used to treat many types of solid and hematological malignancies. Unfortunately, clinical usage of doxorubicin is limited due to the associated acute and chronic cardiotoxicity. Previous studies demonstrated that Astragalus polysaccharide (APS), the extracts of Astragalus membranaceus, had strong anti-tumor activities and anti-inflammatory effects. However, whether APS could mitigate chemotherapy-induced cardiotoxicity is unclear thus far. We used a doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart failure model to explore the function of APS...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901468/loss-of-frataxin-activates-the-iron-sphingolipid-pdk1-mef2-pathway-in-mammals
#20
Kuchuan Chen, Tammy Szu-Yu Ho, Guang Lin, Kai Li Tan, Matthew N Rasband, Hugo J Bellen
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by mutations in Frataxin (FXN). Loss of FXN causes impaired mitochondrial function and iron homeostasis. An elevated production of reactive oxygen species (ROS) was previously proposed to contribute to the pathogenesis of FRDA. We recently showed that loss of frataxin homolog (fh), a Drosophila homolog of FXN, causes a ROS independent neurodegeneration in flies (Chen et al., 2016). In fh mutants, iron accumulation in the nervous system enhances the synthesis of sphingolipids, which in turn activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2) to trigger neurodegeneration of adult photoreceptors...
November 30, 2016: ELife
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