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https://www.readbyqxmd.com/read/28320043/effects-of-ranolazine-in-a-model-of-doxorubicin-induced-left-ventricle-diastolic-dysfunction
#1
Donato Cappetta, Grazia Esposito, Raffaele Coppini, Elena Piegari, Rosa Russo, Loreta Pia Ciuffreda, Alessia Rivellino, Lorenzo Santini, Concetta Rafaniello, Cristina Scavone, Francesco Rossi, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
BACKGROUND AND PURPOSE: Doxorubicin (DOXO) is a highly effective anticancer drug but its clinical application is impeded by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of DOXO cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent late cardiotoxicity is warranted. Increased DOXO-dependent reactive oxygen species may explain, in part, Ca(2+) and Na(+) overload that contributes to diastolic dysfunction and development of heart failure...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28292875/in-vivo-ca-2-dynamics-induced-by-ca-2-injection-in-individual-rat-skeletal-muscle-fibers
#2
Mario Wakizaka, Hiroaki Eshima, Yoshinori Tanaka, Hideki Shirakawa, David C Poole, Yutaka Kano
In contrast to cardiomyocytes, store overload-induced calcium ion (Ca(2+)) release (SOICR) is not considered to constitute a primary Ca(2+) releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage-induced Ca(2+) release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca(2+) concentration ([Ca(2+)]i) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca(2+) microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca(2+)]i dynamics following Ca(2+) injection would be amplified and fiber contraction facilitated by SOICR...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28290590/the-ca-2-atpase-pump-facilitates-bidirectional-proton-transport-across-the-sarco-endoplasmic-reticulum
#3
L Michel Espinoza-Fonseca
Ca(2+) transport across the sarco/endoplasmic reticulum (SR) plays an essential role in intracellular Ca(2+) homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca(2+) uptake and release, proton fluxes are required to balance the charge deficit generated by the exchange of Ca(2+) and other ions across the SR. During Ca(2+) uptake by the SR Ca(2+)-ATPase (SERCA), two protons are countertransported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca(2+) transport...
March 14, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28287621/restoring-the-impaired-cardiac-calcium-homeostasis-and-cardiac-function-in-iron-overload-rats-by-the-combined-deferiprone-and-n-acetyl-cysteine
#4
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Siriporn C Chattipakorn, Nipon Chattipakorn
Intracellular calcium [Ca(2+)]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284503/renal-denervation-regulates-the-atrial-arrhythmogenic-substrates-through-reverse-structural-remodeling-in-heart-failure-rabbit-model
#5
Shinya Yamada, Li-Wei Lo, Yu-Hui Chou, Wei-Lun Lin, Shih-Lin Chang, Yenn-Jiang Lin, Shih-Ann Chen
BACKGROUND: Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. METHODS: Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN...
February 24, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28278204/sarcolipin-deletion-exacerbates-soleus-muscle-atrophy-and-weakness-in-phospholamban-overexpressing-mice
#6
Val A Fajardo, Daniel Gamu, Andrew Mitchell, Darin Bloemberg, Eric Bombardier, Paige J Chambers, Catherine Bellissimo, Joe Quadrilatero, A Russell Tupling
Sarcolipin (SLN) and phospholamban (PLN) are two small proteins that regulate the sarco(endo)plasmic reticulum Ca2+-ATPase pumps. In a recent study, we discovered that Pln overexpression (PlnOE) in slow-twitch type I skeletal muscle fibers drastically impaired SERCA function and caused a centronuclear myopathy-like phenotype, severe muscle atrophy and weakness, and an 8 to 9-fold upregulation of SLN protein in the soleus muscles. Here, we sought to determine the physiological role of SLN upregulation, and based on its role as a SERCA inhibitor, we hypothesized that it would represent a maladaptive response that contributes to the SERCA dysfunction and the overall myopathy observed in the PlnOE mice...
2017: PloS One
https://www.readbyqxmd.com/read/28275147/localization-and-characterization-of-cyp76ae2-part-of-thapsigargin-biosynthesis-in-thapsia-garganica
#7
Trine Bundgaard Andersen, Karen Agatha Martinez-Swatson, Silas Anselm Rasmussen, Berin Alain Boughton, Kirsten Jørgensen, Johan Andersen-Ranberg, Nils Nyberg, Søren Brøgger Christensen, Henrik Toft Simonsen
The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as Deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the SERCA calcium pump in mammals, and is of industrial importance as the active moiety of the anticancer drug Mipsagargin, currently in clinical trials. Knowledge of thapsigargin in planta storage and biosynthesis has so far been limited. Here we present the putative second step in thapsigargin biosynthesis, by showing that the cytochrome P450 TgCYP76AE2, transiently expressed in Nicotiana benthamiana, converts epikunzeaol into epidihydrocostunolide...
March 8, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28270843/liraglutide-directly-protects-cardiomyocytes-against-reperfusion-injury-possibly-via-modulation-of-intracellular-calcium-homeostasis
#8
Shun-Ying Hu, Ying Zhang, Ping-Jun Zhu, Hao Zhou, Yun-Dai Chen
BACKGROUND: Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglutide can perform direct protective effects on cardiomyocytes against reperfusion injury. METHODS: In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation (H/R) induction...
January 2017: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28261092/screening-for-small-molecule-inhibitors-of-statin-induced-app-c-terminal-toxic-fragment-production
#9
Karen S Poksay, Douglas J Sheffler, Patricia Spilman, Jesus Campagna, Barbara Jagodzinska, Olivier Descamps, Olivia Gorostiza, Alex Matalis, Michael Mullenix, Dale E Bredesen, Nicholas D P Cosford, Varghese John
Alzheimer's disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28255076/beneficial-effect-of-renal-denervation-on-ventricular-premature-complex-induced-cardiomyopathy
#10
Shinya Yamada, Li-Wei Lo, Yu-Hui Chou, Wei-Lun Lin, Shih-Lin Chang, Yenn-Jiang Lin, Shin-Huei Liu, Wen-Han Cheng, Tsung-Ying Tsai, Shih-Ann Chen
BACKGROUND: Frequent ventricular premature complexes (VPCs) can lead to the development of dilated cardiomyopathy and sudden cardiac death. Renal artery sympathetic denervation (RDN) may protect the heart from remodeling. This study aimed to investigate the effect of frequent VPCs on structural and electrical properties and whether RDN can protect the heart from remodeling. METHODS AND RESULTS: Eighteen rabbits were randomized to control (n=6), VPC (n=6), and VPC-RDN (n=6) groups...
March 2, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28254579/resveratrol-induced-autophagy-is-dependent-on-ip3rs-and-on-cytosolic-ca-2
#11
Tomas Luyten, Kirsten Welkenhuyzen, Gemma Roest, Elzbieta Kania, Liwei Wang, Mart Bittremieux, David I Yule, Jan B Parys, Geert Bultynck
Previous work revealed that intracellular Ca(2+) signals and the inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) are essential to increase autophagic flux in response to mTOR inhibition, induced by either nutrient starvation or rapamycin treatment. Here, we investigated whether autophagy induced by resveratrol, a polyphenolic phytochemical reported to trigger autophagy in a non-canonical way, also requires IP3Rs and Ca(2+) signaling. Resveratrol augmented autophagic flux in a time-dependent manner in HeLa cells...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28249687/activation-of-endoplasmic-reticulum-calcium-leak-by-2-apb-depends-on-the-luminal-calcium-concentration
#12
Daniel Leon-Aparicio, Jesus Chavez-Reyes, Agustin Guerrero-Hernandez
It has been shown that 2-APB is a nonspecific modulator of ion channel activity, while most of the channels are inhibited by this compound, there are few examples of channels that are activated by 2-APB. Additionally, it has been shown that, 2-APB leads to a reduction in the luminal endoplasmic reticulum Ca(2+) level ([Ca(2+)]ER) and we have carried out simultaneous recordings of both [Ca(2+)]i and the [Ca(2+)]ER in HeLa cell suspensions to assess the mechanism involved in this effect. This approach allowed us to determine that 2-APB induces a reduction in the [Ca(2+)]ER by activating an ER-resident Ca(2+) permeable channel more than by inhibiting the activity of SERCA pumps...
February 8, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28246293/a-whole-genome-rna-interference-screen-reveals-a-role-for-spry2-in-insulin-transcription-and-the-unfolded-protein-response
#13
Zachary Pappalardo, Deeksha G Chopra, Thomas G Hennings, Hunter Richards, Justin Choe, Katherine Yang, Luc Baeyens, Kenny Ang, Steven Chen, Michelle Arkin, Michael S German, Michael T McManus, Gregory M Ku
Insulin production by the pancreatic beta cell is required for normal glucose homeostasis. While key transcription factors that bind to the insulin promoter are known, relatively little is known about the upstream regulators of insulin transcription. Using a whole genome RNA interference screen, we uncovered 26 novel regulators of insulin transcription that regulate diverse processes including oxidative phosphorylation, vesicle traffic, and the unfolded protein response(UPR). We focused on Spry2 -- a gene implicated in human type 2 diabetes by genome wide association studies but without a clear connection to glucose homeostasis...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#14
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
February 24, 2017: Peptides
https://www.readbyqxmd.com/read/28238269/long-acting-pde5-inhibitor-tadalafil-prevents-early-doxorubicin-induced-left-ventricle-diastolic-dysfunction-in-juvenile-mice-potential-role-of-cytoskeletal-proteins
#15
Mohamed Nagiub, Scott Filippone, David Durrant, Anindita Das, Rakesh C Kukreja
The chemotherapeutic use of doxorubicin (Dox) is hindered due to the development of irreversible cardiotoxicity. Specifically, childhood cancer survivors are at greater risk of Dox-induced cardiovascular complications. Because of the potent cardioprotective effect of phosphodiesterase 5 (PDE5) inhibitors, we examined the effect of long-acting PDE5 inhibitor tadalafil (Tada) against Dox cardiotoxicity in juvenile mice. C57BL/6J mice (6 weeks old) were treated with Dox (20 mg/kg, i.v.) and (or) Tada (10 mg/kg daily for 14 days, p...
March 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28237334/functional-involvement-of-protein-kinase-c-rho-kinase-and-trpc3-decreases-while-plc-increases-with-advancement-of-pregnancy-in-mediating-oxytocin-induced-myometrial-contractions-in-water-buffaloes-bubalus-bubalis
#16
Abhishek Sharma, Udayraj P Nakade, Soumen Choudhury, Satish Kumar Garg
Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28223472/overexpression-of-sarcoendoplasmic-reticulum-calcium-atpase-2a-promotes-cardiac-sympathetic-neurotransmission-via-abnormal-endoplasmic-reticulum-and-mitochondria-ca-2-regulation
#17
Julia Shanks, Neil Herring, Errin Johnson, Kun Liu, Dan Li, David J Paterson
Reduced cardiomyocyte excitation-contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague-Dawley, Wistar Kyoto, and spontaneously hypertensive rats...
February 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28222421/luteolin-enhances-sarcoplasmic-reticulum-ca2-atpase-activity-through-p38-mapk-signaling-thus-improving-rat-cardiac-function-after-ischemia-reperfusion
#18
Shasha Zhu, Tongda Xu, Yuanyuan Luo, Yingying Zhang, Haochen Xuan, Yanfeng Ma, Defeng Pan, Dongye Li, Hong Zhu
BACKGROUND/AIMS: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. METHODS: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28218221/gene-expressions-underlying-mishandled-calcium-clearance-and-elevated-generation-of-reactive-oxygen-species-in-the-coronary-artery-smooth-muscle-cells-of-chronic-heart-failure-rats
#19
Liang Ding, Xian-Xiu Su, Wen-Hui Zhang, Yu-Xiang Xu, Xue-Feng Pan
BACKGROUND: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. METHODS: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#20
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
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