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heart and endoplasmic reticulum

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https://www.readbyqxmd.com/read/28801668/exercise-leads-to-unfavourable-cardiac-remodelling-and-enhanced-metabolic-homeostasis-in-obese-mice-with-cardiac-and-skeletal-muscle-autophagy-deficiency
#1
Zhen Yan, Ana Kronemberger, Jay Blomme, Jarrod A Call, Hannah M Caster, Renata O Pereira, Henan Zhao, Vitor U de Melo, Rhianna C Laker, Mei Zhang, Vitor A Lira
Autophagy is stimulated by exercise in several tissues; yet the role of skeletal and cardiac muscle-specific autophagy on the benefits of exercise training remains incompletely understood. Here, we determined the metabolic impact of exercise training in obese mice with cardiac and skeletal muscle disruption of the Autophagy related 7 gene (Atg7(h&mKO)). Muscle autophagy deficiency did not affect glucose clearance and exercise capacity in lean adult mice. High-fat diet in sedentary mice led to endoplasmic reticulum stress and aberrant mitochondrial protein expression in autophagy-deficient skeletal and cardiac muscles...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801645/chronic-intermittent-hypobaric-hypoxia-improves-cardiac-function-through-inhibition-of-endoplasmic-reticulum-stress
#2
Fang Yuan, Li Zhang, Yan-Qing Li, Xu Teng, Si-Yu Tian, Xiao-Ran Wang, Yi Zhang
We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794819/upregulation-of-autophagy-genes-and-the-unfolded-protein-response-in-human-heart-failure
#3
Brian C Jensen, Scott J Bultman, Darcy Holley, Wei Tang, Gustaaf de Ridder, Salvatore Pizzo, Dawn Bowles, Monte S Willis
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1...
2017: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28768233/identification-of-transcriptome-signature-for-myocardial-reductive-stress
#4
Justin M Quiles, Madhusudhanan Narasimhan, Timothy Mosbruger, Gobinath Shanmugam, David Crossman, Namakkal S Rajasekaran
The nuclear factor erythroid 2 like 2 (Nfe2l2/Nrf2) is a master regulator of antioxidant gene transcription. We recently identified that constitutive activation of Nrf2 (CaNrf2) caused reductive stress (RS) in the myocardium. Here we investigate how chronic Nrf2 activation alters myocardial mRNA transcriptome in the hearts of CaNrf2 transgenic (TG-low and TG-high) mice using an unbiased integrated systems approach and next generation RNA sequencing followed by qRT-PCR methods. A total of 246 and 1031 differentially expressed genes (DEGs) were identified in the heart of TGL and TGH in relation to NTG littermates at ~ 6 months of age...
July 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28767701/cardiac-directed-expression-of-a-catalytically-inactive-adenylyl-cyclase-6-protects-the-heart-from-sustained-%C3%AE-adrenergic-stimulation
#5
Mei Hua Gao, N Chin Lai, Dimosthenis Giamouridis, Young Chul Kim, Tracy Guo, H Kirk Hammond
OBJECTIVES: Increased expression of adenylyl cyclase type 6 (AC6) has beneficial effects on the heart through cyclic adenosine monophosphate (cAMP)-dependent and cAMP-independent pathways. We previously generated a catalytically inactive mutant of AC6 (AC6mut) that has an attenuated response to β-adrenergic receptor stimulation, and, consequently, exhibits reduced myocardial cAMP generation. In the current study we test the hypothesis that cardiac-directed expression of AC6mut would protect the heart from sustained β-adrenergic receptor stimulation, a condition frequently encountered in patients with heart failure...
2017: PloS One
https://www.readbyqxmd.com/read/28757580/role-of-mitochondria-and-endoplasmic-reticulum-in-taurine-deficiency-mediated-apoptosis
#6
Chian Ju Jong, Takashi Ito, Howard Prentice, Jang-Yen Wu, Stephen W Schaffer
Taurine is a ubiquitous sulfur-containing amino acid found in high concentration in most tissues. Because of its involvement in fundamental physiological functions, such as regulating respiratory chain activity, modulating cation transport, controlling inflammation, altering protein phosphorylation and prolonging lifespan, taurine is an important nutrient whose deficiency leads to severe pathology and cell death. However, the mechanism by which taurine deficiency causes cell death is inadequately understood...
July 25, 2017: Nutrients
https://www.readbyqxmd.com/read/28753907/shikonin-ameliorates-isoproterenol-iso-induced-myocardial-damage-through-suppressing-fibrosis-inflammation-apoptosis-and-er-stress
#7
Jun Yang, Zhao Wang, Dong-Lin Chen
Shikonin, isolated from the roots of herbal plant Lithospermum erythrorhizon, is a naphthoquinone. It has been reported to exert beneficial anti-inflammatory effects and anti-oxidant properties in various diseases. Isoproterenol (ISO) has been widely used to establish cardiac injury in vivo and in vitro. However, shikonin function in ISO-induced cardiac injury remains uncertain. In our study, we attempted to investigate the efficiency and possible molecular mechanism of shikonin in cardiac injury treatment induced by ISO...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28748322/schisandrin-b-ameliorates-myocardial-ischemia-reperfusion-injury-through-attenuation-of-endoplasmic-reticulum-stress-induced-apoptosis
#8
Wei Zhang, Zhiqing Sun, Fanhua Meng
Schisandrin B (Sch B), an active composition isolated from the fruit of Schisandra chinensis, has been proved to possess antiinflammatory, antioxidant and anti-endoplasmic reticulum (ER) stress effects in many rodent tissues. However, the exact mechanism of cardioprotective effect of Sch B still needs more study. Here, we detected the effects of Sch B on myocardial ischemia/reperfusion (I/R) injury rats. I/R injury model in this study was established by left anterior descending coronary artery ligation for 40 min followed by 1 h of reperfusion...
July 26, 2017: Inflammation
https://www.readbyqxmd.com/read/28743963/a-non-canonical-pathway-regulates-er-stress-signaling-and-blocks-er-stress-induced-apoptosis-and-heart-failure
#9
Yufeng Yao, Qiulun Lu, Zhenkun Hu, Yubin Yu, Qiuyun Chen, Qing K Wang
Endoplasmic reticulum stress is an evolutionarily conserved cell stress response associated with numerous diseases, including cardiac hypertrophy and heart failure. The major endoplasmic reticulum stress signaling pathway causing cardiac hypertrophy involves endoplasmic reticulum stress sensor PERK (protein kinase-like kinase) and eIF2α-ATF4-CHOP signaling. Here, we describe a non-canonical, AGGF1-mediated regulatory system for endoplasmic reticulum stress signaling associated with increased p-eIF2α and ATF4 and decreased sXBP1 and CHOP...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#10
Manami Kaneko, Hisato Yamamoto, Hiroki Sakai, Yusuke Kamada, Toshiki Tanaka, Shuji Fujiwara, Synsuke Yamamoto, Hiroki Takahagi, Hideyuki Igawa, Shizuo Kasai, Masakuni Noda, Makoto Inui, Tomoyuki Nishimoto
The cardiac sarco/endoplasmic reticulum Ca(2+)-dependent ATPase 2a (SERCA2a) plays a central role in Ca(2+) handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca(2+)-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28713984/downregulation-of-microrna%C3%A2-199a%C3%A2-5p-protects-cardiomyocytes-in-cyanotic-congenital-heart-disease-by-attenuating-endoplasmic-reticulum-stress
#11
Yang Zhou, Wei-Kun Jia, Zhao Jian, Liang Zhao, Chen-Cheng Liu, Yong Wang, Ying-Bin Xiao
Chronic hypoxia is a key pathological change in patients with cyanotic congenital heart defect (CCHD). It has been demonstrated that enhanced myocardial unfolded protein response (UPR) increases the capacity to buffer endoplasmic reticulum (ER) stress and to avoid subsequent apoptosis caused by the hypoxia that underlies CCHD. The present study was performed to determine the regulatory role of microRNAs (miRNAs) in this cytoprotective UPR process. The results revealed that miR‑199a‑5p was markedly downregulated in the cardiac tissue of patients with CCHD and in human myocardial cells cultured in hypoxic conditions...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28700997/nobiletin-a-polymethoxy-flavonoid-protects-against-cardiac-hypertrophy-induced-by-pressure-overload-via-inhibition-of-napdh-oxidases-and-endoplasmic-reticulum-stress
#12
Ning Zhang, Wen-Ying Wei, Zheng Yang, Yan Che, Ya-Ge Jin, Hai-Han Liao, Sha-Sha Wang, Wei Deng, Qi-Zhu Tang
BACKGROUND/AIMS: An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB), extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. METHODS: Mice received aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/SH), sham+NOB (NOB/SH), AB+vehicle (VEH/AB), and AB+ NOB (NOB/AB)...
July 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28681937/maternal-nicotine-exposure-leads-to-decreased-cardiac-protein-disulfide-isomerase-and-impaired-mitochondrial-function-in-male-rat-offspring
#13
Nicole G Barra, Maria Lisyansky, Taylor A Vanduzer, Sandeep Raha, Alison C Holloway, Daniel B Hardy
Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood...
July 6, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28664743/mapk-pathway-regulated-the-cardiomyocyte-apoptosis-in-mice-with-post-infarction-heart-failure
#14
Q Zhang, L Lu, T Liang, M Liu, Z L Wang, P Y Zhang
BACKGROUND: To explore the role of the MAPK signaling pathway in the cardiomyocyte apoptosis of mice with post-infarction heart failure (HF). METHODS: Mice were divided into sham and myocardial infarction (MI) groups. Before surgery, the MI group was divided into SB203580 and PBS subgroups. A post-infarction HF model was established by ligating the left anterior descending coronary artery. Ventricular dilatation and cardiac function were observed by small animal echocardiography...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28664677/comparative-evaluation-of-torasemide-and-spironolactone-on-adverse-cardiac-remodeling-in-a-rat-model-of-dilated-cardiomyopathy
#15
Somasundaram Arumugam, Remya Sreedhar, Vengadeshprabhu Karuppagounder, Meilei Harima, Masahiko Nakamura, Hiroshi Suzuki, Hirohito Sone, Kenichi Watanabe
BACKGROUND: Chronic heart failure (CHF) involves fluid retention and volume overload, leading to impaired cardiac function. In these conditions, diuretic agents are most commonly used to treat edema and thereby reducing the volume load on the failing heart. There are several other beneficial effects of diuretics apart from their action on urinary excretion. METHODS: In order to identify the effects of diuretic agents on adverse cardiac remodeling in CHF, the present study was carried out, where we have compared the effects of torasemide and spironolactone in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28630914/deregulated-ca-2-cycling-underlies-the-development-of-arrhythmia-and-heart-disease-due-to-mutant-obscurin
#16
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/28620033/scissor-sisters-regulation-of-adam10-by-the-tspanc8-tetraspanins
#17
REVIEW
Alexandra L Matthews, Justyna Szyroka, Richard Collier, Peter J Noy, Michael G Tomlinson
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane protein which is essential for embryonic development through activation of Notch proteins. ADAM10 regulates over 40 other transmembrane proteins and acts as a 'molecular scissor' by removing their extracellular regions. ADAM10 is also a receptor for α-toxin, a major virulence factor of Staphylococcus aureus Owing to the importance of its substrates, ADAM10 is a potential therapeutic target for cancer, neurodegenerative diseases such as Alzheimer's and prion diseases, bacterial infection and inflammatory diseases such as heart attack, stroke and asthma...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28611075/identification-and-functional-characterization-of-hypoxia-induced-endoplasmic-reticulum-stress-regulating-lncrna-hyperlnc-in-pericytes
#18
Florian C Bischoff, Astrid Werner, David John, Jes-Niels Boeckel, Maria-Theodora Melissari, Phillip Grote, Simone F Glaser, Shemsi Demolli, Shizuka Uchida, Katharina M Michalik, Benjamin Meder, Hugo A Katus, Jan Haas, Wei Chen, Soni S Pullamsetti, Werner Seeger, Andreas M Zeiher, Stefanie Dimmeler, Christoph M Zehendner
Rationale: Pericytes are essential for vessel maturation and endothelial barrier function. Long non-coding RNAs (lncRNAs) regulate many cellular functions, but their role in pericyte biology remains unexplored. Objective: Here we investigate the effect of Hypoxia-Induced Endoplasmic Reticulum Stress Regulating lncRNA (HypERlnc, also known as ENSG00000262454) on pericyte function in vitro and its regulation in human heart failure and idiopathic pulmonary arterial hypertension. Methods and Results: RNA sequencing in human primary pericytes (hPCs) identified hypoxia regulated lncRNAs, including HypERlnc...
June 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28597987/trafficking-and-localization-to-the-plasma-membrane-of-nav-1-5-promoted-by-the-%C3%AE-2-subunit-is-defective-due-to-a-%C3%AE-2-mutation-associated-with-brugada-syndrome
#19
Gemma Dulsat, Sonia Palomeras, Eric Cortada, Helena Riuró, Ramon Brugada, Marcel Vergés
BACKGROUND INFORMATION: Cardiac channelopathies arise by mutations in genes encoding ion channel subunits. One example is Brugada Syndrome (BrS), which causes arrhythmias and sudden death. BrS is often associated with mutations in SCN5A, encoding Nav 1.5, the α subunit of the major cardiac voltage-gated sodium channel. This channel forms a protein complex including one or two associated β subunits as well as other proteins. RESULTS: We analyzed regulation of Nav 1...
June 9, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28597249/differential-regulation-of-protein-phosphatase-1-pp1-isoforms-in-human-heart-failure-and-atrial-fibrillation
#20
Stefanie Meyer-Roxlau, Simon Lämmle, Annett Opitz, Stephan Künzel, Julius P Joos, Stefan Neef, Karolina Sekeres, Samuel Sossalla, Friedrich Schöndube, Konstantin Alexiou, Lars S Maier, Dobromir Dobrev, Kaomei Guan, Silvio Weber, Ali El-Armouche
Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression...
July 2017: Basic Research in Cardiology
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