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https://www.readbyqxmd.com/read/28826496/the-calcineurin-foxo-murf1-signaling-pathway-regulates-myofibril-integrity-in-cardiomyocytes
#1
Hirohito Shimizu, Adam D Langenbacher, Jie Huang, Kevin Wang, Georg Otto, Robert Geisler, Yibin Wang, Jau-Nian Chen
Altered Ca(2+) handling is often present in diseased hearts undergoing structural remodeling and functional deterioration. However, whether Ca(2+) directly regulates sarcomere structure has remained elusive. Using a zebrafish ncx1 mutant, we explored the impacts of impaired Ca(2+) homeostasis on myofibril integrity. We found that the E3 ubiquitin ligase murf1 is upregulated in ncx1-deficient hearts. Intriguingly, knocking down murf1 activity or inhibiting proteasome activity preserved myofibril integrity, revealing a MuRF1-mediated proteasome degradation mechanism that is activated in response to abnormal Ca(2+) homeostasis...
August 19, 2017: ELife
https://www.readbyqxmd.com/read/28817785/diving-into-the-world-of-alcohol-teratogenesis-a-review-of-zebrafish-models-of-fetal-alcohol-spectrum-disorders
#2
Yohaan Fernandes, Desirè M Buckley, Johann K Eberhart
Fetal alcohol spectrum disorders (FASD) refer to the entire suite of deleterious outcomes resulting from embryonic alcohol exposure. Along with other reviews in this edition, we provide insight into how animal models, specifically the zebrafish; have informed our understanding of FASD. We first provide a brief introduction to FASD. We discuss the zebrafish as a model organism and its strengths for alcohol research. We detail how zebrafish has been used to model some of the major defects present in FASD. These include behavioral defects, such as social behavior as well as learning and memory, and structural defects, disrupting organs such as the brain, sensory organs, heart and craniofacial skeleton...
August 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28807900/heart-morphogenesis-gene-regulatory-networks-revealed-by-temporal-expression-analysis
#3
Jonathon T Hill, Bradley Demarest, Megan Smith, Bushra Gorsi, H Joseph Yost
During embryogenesis, the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq time course in zebrafish from 30 hpf to 72 hpf and identified 5,861 genes with altered expression. We then clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28803741/the-cardiovascular-toxicity-of-triadimefon-in-early-life-stage-of-zebrafish-and-potential-implications-to-human-health
#4
Hong-Cui Liu, Tian-Yi Chu, Li-Li Chen, Wen-Jun Gui, Guo-Nian Zhu
The health risk of triadimefon (TF) to cardiovascular system of human is still unclear, especially to pesticide suicides population, occupational population (farmers, retailers and pharmaceutical workers), and special population (young children and infants, pregnant women, older people, and those with compromised immune systems) who are at a greater risk. Therefore, firstly we explored the toxic effects and possible mechanism of cardiovascular toxicity induced by TF using zebrafish model. Zebrafish at stage of 48 h post fertilization (hpf) exposed to TF for 24 h exhibited morphological malformations which were further confirmed by histopathologic examination, including pericardial edema, circulation abnormalities, serious venous thrombosis and increased distance between the sinus venosus (SV) and bulbus arteriosus (BA) regions of the heart...
August 10, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28803248/a-functional-assay-for-sick-sinus-syndrome-genetic-variants
#5
Chuanchau J Jou, Cammon B Arrington, Spencer Barnett, Jiaxiang Shen, Scott Cho, Xiaoming Sheng, Patrick C McCullagh, Neil E Bowles, Chase M Pribble, Elizabeth V Saarel, Thomas A Pilcher, Susan P Etheridge, Martin Tristani-Firouzi
BACKGROUND/AIMS: Congenital Sick Sinus Syndrome (SSS) is a disorder associated with sudden cardiac death due to severe bradycardia and prolonged pauses. Mutations in HCN4, the gene encoding inward Na+/K+ current (If), have been described as a cause of congenital SSS. The objective of this study is to develop an SSS model in embryonic zebrafish, and use zebrafish as a moderate-throughput assay to functionally characterize HCN4 variants. METHODS: To determine the function of hcn4 in zebrafish, embryos were either bathed in the If -specific blocker (ZD-7288), or endogenous hcn4 expression was knocked down using splice-blocking morpholinos...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28801532/activation-of-nkx2-5-calr-p53-signaling-pathway-by-hyperglycemia-induces-cardiac-remodeling-and-dysfunction-in-adult-zebrafish
#6
Sun Yanyi, Wang Qiuyun, Fang Yuehua, Wu Chunfang, Lu Guoping, Chen Zhenyue
Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia...
August 11, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28783163/frequency-of-mononuclear-diploid-cardiomyocytes-underlies-natural-variation-in-heart-regeneration
#7
Michaela Patterson, Lindsey Barske, Ben Van Handel, Christoph D Rau, Peiheng Gan, Avneesh Sharma, Shan Parikh, Matt Denholtz, Ying Huang, Yukiko Yamaguchi, Hua Shen, Hooman Allayee, J Gage Crump, Thomas I Force, Ching-Ling Lien, Takako Makita, Aldons J Lusis, S Ram Kumar, Henry M Sucov
Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content...
August 7, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28772162/acute-exposure-to-tris-2-butoxyethyl-phosphate-tboep-affects-growth-and-development-of-embryo-larval-zebrafish
#8
Yiran Liu, Ding Wu, Qinglong Xu, Liqin Yu, Chunsheng Liu, Jianghua Wang
Tris (2-butoxyethyl) phosphate (TBOEP), is used as a flame retardant worldwide. It is an additive in materials and can be easily discharged into the surrounding environment. There is evidence linking TBOEP exposure to abnormal development and growth in zebrafish embryos/larvae. Here, using zebrafish embryo as a model, we investigated toxicological effects on developing zebrafish (Danio rerio) caused by TBOEP at concentrations of 0, 20, 200, 1000, 2000μg/L starting from 2h post-fertilization (hpf). Our findings revealed that TBOEP exposure caused developmental toxicity, such as malformation, growth delay and decreased heart rate in zebrafish larvae...
July 27, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28771527/claudin5a-is-required-for-proper-inflation-of-kupffer-s-vesicle-lumen-and-organ-laterality
#9
Jeong-Gyun Kim, Sung-Jin Bae, Hye Shin Lee, Ji-Hyeon Park, Kyu-Won Kim
Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer's vesicle (KV) is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a) is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen...
2017: PloS One
https://www.readbyqxmd.com/read/28771499/irisin-regulates-cardiac-physiology-in-zebrafish
#10
Lakshminarasimhan Sundarrajan, Chanel Yeung, Logan Hahn, Lynn P Weber, Suraj Unniappan
Irisin is a myokine encoded in its precursor fibronectin type III domain containing 5 (FNDC5). It is abundantly expressed in cardiac and skeletal muscle, and is secreted upon the activation of peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1 alpha). We aimed to study the role of irisin on cardiac function and muscle protein regulation in zebrafish. Western blot analyses detected the presence of irisin protein (23 kDa) in zebrafish heart and skeletal muscle, and irisin immunoreactivity was detected in both tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28767718/zygotic-vinculin-is-not-essential-for-embryonic-development-in-zebrafish
#11
Mitchell K L Han, Gerard N M van der Krogt, Johan de Rooij
The formation of multicellular tissues during development is governed by mechanical forces that drive cell shape and tissue architecture. Protein complexes at sites of adhesion to the extracellular matrix (ECM) and cell neighbors, not only transmit these mechanical forces, but also allow cells to respond to changes in force by inducing biochemical feedback pathways. Such force-induced signaling processes are termed mechanotransduction. Vinculin is a central protein in mechanotransduction that in both integrin-mediated cell-ECM and cadherin-mediated cell-cell adhesions mediates force-induced cytoskeletal remodeling and adhesion strengthening...
2017: PloS One
https://www.readbyqxmd.com/read/28762163/polycystin-2-dependent-cardio-protective-mechanisms-revealed-by-cardiac-stress
#12
Esther Giehl, Fernanda O Lemos, Yan Huang, Frank J Giordano, Ivana Y Kuo, Barbara E Ehrlich
Although autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple kidney cysts, the most frequent cause of death in ADPKD patients is cardiovascular disease. ADPKD is linked to mutations in PKD1 or pkd2, the genes that encode for the proteins polycystin 1 and polycystin 2 (PC1 and PC2, respectively). The cardiovascular complications have been assumed to be a consequence of renal hypertension and activation of renin/angiotensin/aldosterone (RAAS) pathway. However, the expression of PC1 and PC2 in cardiac tissue suggests additional direct effects of these proteins on cardiac function...
July 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28761722/a-tbx5-3-utr-variant-increases-the-risk-of-congenital-heart-disease-in-the-han-chinese-population
#13
Feng Wang, Dong Liu, Ran-Ran Zhang, Li-Wei Yu, Jian-Yuan Zhao, Xue-Yan Yang, Song-Shan Jiang, Duan Ma, Bin Qiao, Feng Zhang, Li Jin, Yong-Hao Gui, Hong-Yan Wang
TBX5 is a vital transcription factor involved in cardiac development in a dosage-dependent manner. But little is known about the potential association of TBX5 3' untranslated region (UTR) variations with congenital cardiac malformations. This study aimed to investigate the relationship between TBX5 3'UTR variants and risk for congenital heart disease (CHD) susceptibility in two Han Chinese populations, and to reveal its molecular mechanism. The relationship between TBX5 3'UTR variants and CHD susceptibility was examined in 1 177 CHD patients and 990 healthy controls in two independent case-control studies...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28757278/distribution-and-chronotropic-effects-of-serotonin-in-the-zebrafish-heart
#14
Matthew R Stoyek, Michael G Jonz, Frank M Smith, Roger P Croll
Several lines of evidence suggest that serotonin (5-HT) has a regulatory role in cardiovascular function from embryogenesis through adulthood. However, the reported actions of 5-HT are often contradictory and include bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction. Clarifying such cardiac effects requires further research and may benefit from utilizing a model simpler than the mammalian hearts traditionally used in these studies. In the present study, we describe the cardiac distribution and chronotropic responses of 5-HT in the zebrafish heart...
September 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28753627/nuclear-cytoplasmic-transport-defects-in-bbs6-underlie-congenital-heart-disease-through-perturbation-of-a-chromatin-remodeling-protein
#15
Charles Anthony Scott, Autumn N Marsden, Michael R Rebagliati, Qihong Zhang, Xitiz Chamling, Charles C Searby, Lisa M Baye, Val C Sheffield, Diane C Slusarski
Mutations in BBS6 cause two clinically distinct syndromes, Bardet-Biedl syndrome (BBS), a syndrome caused by defects in cilia transport and function, as well as McKusick-Kaufman syndrome, a genetic disorder characterized by congenital heart defects. Congenital heart defects are rare in BBS, and McKusick-Kaufman syndrome patients do not develop retinitis pigmentosa. Therefore, the McKusick-Kaufman syndrome allele may highlight cellular functions of BBS6 distinct from the presently understood functions in the cilia...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28743586/intrinsic-regulation-of-sinoatrial-node-function-and-the-zebrafish-as-a-model-of-stretch-effects-on-pacemaking
#16
REVIEW
Eilidh A MacDonald, Matthew R Stoyek, Robert A Rose, T Alexander Quinn
Excitation of the heart occurs in a specialised region known as the sinoatrial node (SAN). Tight regulation of SAN function is essential for the maintenance of normal heart rhythm and the response to (patho-)physiological changes. The SAN is regulated by extrinsic (central nervous system) and intrinsic (neurons, peptides, mechanics) factors. The positive chronotropic response to stretch in particular is essential for beat-by-beat adaptation to changes in hemodynamic load. Yet, the mechanism of this stretch response is unknown, due in part to the lack of an appropriate experimental model for targeted investigations...
July 22, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28732770/pharmacologic-modeling-of-primary-mitochondrial-respiratory-chain-dysfunction-in-zebrafish
#17
James Byrnes, Rebecca Ganetzky, Richard Lightfoot, Michael Tzeng, Eiko Nakamaru-Ogiso, Christoph Seiler, Marni J Falk
Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology...
July 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28729726/heart-regeneration-and-repair-after-myocardial-infarction-translational-opportunities-for-novel-therapeutics
#18
REVIEW
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28729419/the-exocyst-is-required-for-photoreceptor-ciliogenesis-and-retinal-development
#19
Glenn P Lobo, Diana Fulmer, Lilong Guo, Xiaofeng Zuo, Yujing Dang, Seok-Hyung Kim, Yanhui Su, Kola George, Elisabeth Obert, Ben Fogelgren, Deepak Nihalani, Russell A Norris, Bärbel Rohrer, Joshua H Lipschutz
We previously have shown that the highly-conserved eight-protein exocyst trafficking complex is required for ciliogenesis in kidney tubule cells. We hypothesized here that ciliogenic programs are conserved across organs and species. To determine if renal primary ciliogenic programs are conserved in the eye, and to characterize the function and mechanisms by which the exocyst regulates eye development in zebrafish, we focused on exoc5, a central component of the exocyst complex, by analyzing both exoc5 zebrafish mutants, and photoreceptor-specific Exoc5 knockout mice...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28722335/protective-effects-of-folic-acid-on-pm2-5-induced-cardiac-developmental-toxicity-in-zebrafish-embryos-by-targeting-ahr-and-wnt-%C3%AE-catenin-signal-pathways
#20
Cong Yue, Cheng Ji, Hang Zhang, Leshuai W Zhang, Jian Tong, Yan Jiang, Tao Chen
Our previous observations indicated that extractable organic matter (EOM) from PM2.5 induced malformations in the heart of zebrafish embryos by activating AhR and inhibiting canonical Wnt/β-catenin signal pathway. As a nutritional factor, folic acid (FA) is reported to prevent cardiac defects during embryo development. Hence, we hypothesize that FA may prevent PM2.5-induced heart defects by interfering with AhR and Wnt/β-catenin signaling pathways. Our results showed that FA supplementation alleviated the EOM-induced heart defects in zebrafish embryos, and both AhR inhibitor CH223191 and Wnt activator CHIR99021 enhanced the protective efficiency of FA...
July 19, 2017: Environmental Toxicology
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