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SERCA2a

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https://www.readbyqxmd.com/read/28928601/early-right-ventricular-apical-pacing-induced-gene-expression-alterations-are-associated-with-deterioration-of-left-ventricular-systolic-function
#1
Haiyan Xu, Xiongwei Xie, Jiangjin Li, Yuanyuan Zhang, Changsong Xu, Jing Yang
The chronic high-dose right ventricular apical (RVA) pacing may have deleterious effects on left ventricular (LV) systolic function. We hypothesized that the expression changes of genes regulating cardiomyocyte energy metabolism and contractility were associated with deterioration of LV function in patients who underwent chronic RVA pacing. Sixty patients with complete atrioventricular block and preserved ejection fraction (EF) who underwent pacemaker implantation were randomly assigned to either RVA pacing (n = 30) group or right ventricular outflow tract (RVOT) pacing (n = 30) group...
2017: Disease Markers
https://www.readbyqxmd.com/read/28889229/melatonin-alleviates-inflammation-induced-apoptosis-in-human-umbilical-vein-endothelial-cells-via-suppression-of-ca-2-xo-ros-drp1-mitochondrial-fission-axis-by-activation-of-ampk-serca2a-pathway
#2
Jiasen Cui, Zeng Li, Shunjiu Zhuang, Shaohong Qi, Li Li, Junwen Zhou, Wan Zhang, Yun Zhao
Endothelia inflammation damage is vital to the development and progression of chronic venous disease. In the present study, we explored the protective effect of melatonin on endothelia apoptosis induced by LPS, particularly focusing on the mitochondrial fission. We demonstrated that human umbilical vein endothelial cells (HUVEC) subjected to LPS for 12 h exhibited a higher apoptotic rate. However, melatonin (1-20 μM) treatment 12 h before LPS had the ability to protect HUVEC cell against LPS-mediated apoptosis in a dose-dependent manner...
September 9, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28884444/the-ccaat-box-in-the-proximal-serca2-gene-promoter-regulates-basal-and-stress-induced-transcription-in-cardiomyocytes
#3
Jorge Fragoso-Medina, Gabriela Rodriguez, Angel Zarain-Herzberg
The cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated...
September 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28878117/tead1-is-required-for-maintaining-adult-cardiomyocyte-function-and-its-loss-results-in-lethal-dilated-cardiomyopathy
#4
Ruya Liu, Jeongkyung Lee, Byung S Kim, Qiongling Wang, Samuel K Buxton, Nikhil Balasubramanyam, Jean J Kim, Jianrong Dong, Aijun Zhang, Shumin Li, Anisha A Gupte, Dale J Hamilton, James F Martin, George G Rodney, Cristian Coarfa, Xander Ht Wehrens, Vijay K Yechoor, Mousumi Moulik
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28874462/%C3%AE-arrestin2-improves-post-myocardial-infarction-heart-failure-via-sarco-endo-plasmic-reticulum-ca-2-atpase-dependent-positive-inotropy-in-cardiomyocytes
#5
Katie A McCrink, Jennifer Maning, Angela Vu, Malika Jafferjee, Christine Marrero, Ava Brill, Ashley Bathgate-Siryk, Samalia Dabul, Walter J Koch, Anastasios Lymperopoulos
Heart failure is the leading cause of death in the Western world, and new and innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins βarr (β-arrestin)-1 and βarr-2 are functionally distinct in the heart. βarr1 is cardiotoxic, decreasing contractility by opposing β1AR (adrenergic receptor) signaling and promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, βarr2 inhibits apoptosis/inflammation post-MI but its effects on cardiac function are not well understood...
September 5, 2017: Hypertension
https://www.readbyqxmd.com/read/28811460/prevention-of-atrial-fibrillation-by-using-sarcoplasmic-reticulum-calcium-atpase-pump-overexpression-in-a-rabbit-model-of-rapid-atrial-pacing
#6
Hong Li Wang, Xian Hui Zhou, Zhi Qiang Li, Ping Fan, Qi Na Zhou, Yao Dong Li, Yue Mei Hou, Bao Peng Tang
BACKGROUND Recent research suggests that abnormal Ca2+ handling plays a role in the occurrence and maintenance of atrial fibrillation (AF). Therefore, Ca2+ release and ingestion depend on properties of the ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+ATPase2a (SERCA2a). This study aimed to detect whether SERCA2a gene overexpression has a preventive effect on atrial fibrillation caused by rapid pacing right atrium. MATERIAL AND METHODS Forty-eight New Zealand white rabbits were randomly divided into a control group, AF group, AAV9/GFP group, and AAV9/SERCA2a group...
August 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28807154/total-internal-reflectance-fluorescence-imaging-of-genetically-engineered-ryanodine-receptor-targeted-ca-2-probes-in-rat-ventricular-myocytes
#7
Sara Pahlavan, Marin Morad
The details of cardiac Ca(2+) signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca(2+) probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca(2+) nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, Kd=150nM, or FKBP-GCaMP6, Kd=240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP,(2)-targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28801239/salsalate-activates-skeletal-muscle-thermogenesis-and-protects-mice-from-high-fat-diet-induced-metabolic-dysfunction
#8
Li Nie, Xin-Lu Yuan, Ke-Tao Jiang, Yu-Hui Jiang, Jin Yuan, Lan Luo, Shi-Wei Cui, Cheng Sun
Salsalate plays beneficial roles for ameliorating hyperglycemia and dyslipidemia in type 2 diabetes patients, but the underlying mechanisms are still poorly understood. In this study, by administering salsalate to mice fed with high fat diet and examining how salsalate rectifies metabolic dysfunction in these obese mice, we found that salsalate stimulated body temperature and attenuated body weight gain without affecting food intake. Our results showed that salsalate application decreased lipid accumulation in liver and epididymal white adipose tissue (eWAT), inhibited hepatic gluconeogenesis and improved insulin signaling transduction in eWAT...
August 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28800400/mechanism-of-tfam-mediated-cardiomyocyte-protection
#9
George H Kunkel, Pankaj Chaturvedi, Nicholas Theilen, Rohit Nair, Suresh C Tyagi
Although mitochondrial transcription factor A (TFAM) is a protective component of mitochondrial DNA and a regulator of calcium and reactive oxygen species (ROS) production, the mechanism remains unclear. In heart failure (HF), TFAM is significantly decreased and cardiomyocyte instability ensues. TFAM inhibits Nuclear Factor of Activated T cells (NFAT), which reduces ROS production; additionally, TFAM transcriptionally activates SERCA2a to decrease free calcium. Therefore, decreasing TFAM vastly increases protease expression and hypertrophic factors, leading to cardiomyocyte functional decline...
August 11, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28798077/cardiovascular-susceptibility-to-in-vivo-ischemic-myocardial-injury-in-male-and-female-rat-offspring-exposed-to-prenatal-hypoxia
#10
Amin Shah, Nobutoshi Matsumura, Anita Quon, Jude S Morton, Jason R B Dyck, Sandra T Davidge
Intrauterine growth restriction (IUGR) following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease (CVD) in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring, which experienced normoxia (21% O2) or hypoxia (11% O2) in utero underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia...
September 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28795720/restoring-calcium-homeostasis-in-diabetic-cardiomyocytes-an-investigation-through-mathematical-modelling
#11
Phonindra Nath Das, Ajay Kumar, Nandadulal Bairagi, Samrat Chatterjee
Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium dynamics changes in a cardiomyocyte under diabetic conditions. We proposed and analysed a four dimensional ordinary differential equation (ODE) model to capture the interdependency of calcium dynamics on glucose uptake and ATP generation...
August 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28794003/antenatal-early-postnatal-hypothyroidism-alters-arterial-tone-regulation-in-2-week-old-rats
#12
Svetlana I Sofronova, Dina K Gaynullina, Anastasia A Shvetsova, Anna A Borzykh, Ekaterina K Selivanova, Anna P Sharova, Andrey A Martyanov, Olga S Tarasova
The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO-pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA)...
August 9, 2017: Journal of Endocrinology
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
#13
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/28763488/anthocyanin-rich-extract-of-brassica-oleracea-l-alleviates-experimentally-induced-myocardial-infarction
#14
Sarmita Jana, Dipak Patel, Shweta Patel, Kapil Upadhyay, Jaymesh Thadani, Rahul Mandal, Santasabuj Das, Ranjitsinh Devkar
Cardioprotective potential of anthocyanin rich red cabbage extract (ARCE) was assessed in H2O2 treated rat neonatal cardiomyoblasts (H9c2 cells) and isoproterenol (ISO) induced rodent model of myocardial infarction. H2O2 treated H9c2 cells recorded cytotoxicity (48-50%) and apoptosis (57.3%), the same were reduced in presence of ARCE (7-10% & 12.3% respectively). Rats pretreated with ARCE for 30 days followed by ISO treatment recorded favourable heart: body weight ratio as compared to ISO treated group. Also, the mRNA levels of enzymatic antioxidants (sod and catalase) and apoptotic genes (bax and bcl-2) in ARCE+ISO treated group were similar to the control group suggesting that ARCE pretreatment prevents ISO induced depletion of enzymatic antioxidants and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28750934/serca2a-a-potential-non-invasive-biomarker-of-cardiac-allograft-rejection
#15
Estefanía Tarazón, Ana Ortega, Carolina Gil-Cayuela, Elena Sánchez-Lacuesta, Pilar Marín, Francisca Lago, José Ramón González-Juanatey, Luis Martínez-Dolz, Manuel Portolés, Miguel Rivera, Esther Roselló-Lletí
BACKGROUND: The detection of heart transplant rejection by non-invasive methods remains a major challenge. Despite the well-known importance of the study of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in the heart, its role as a rejection marker has never been analyzed. Our objective in this study was to determine whether circulating SERCA2a could be a good marker of cardiac rejection. METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs) and serum samples from adult heart transplant recipients (49 without allograft rejection and 78 with the diagnosis of biopsy allograft rejection, including 48 Grade 1R, 21 Grade 2R and 9 Grade 3R)...
July 5, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#16
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/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#17
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28670631/cardiac-directed-expression-of-adenylyl-cyclase-catalytic-domain-reverses-cardiac-dysfunction-caused-by-sustained-beta-adrenergic-receptor-stimulation
#18
Mei Hua Gao, N Chin Lai, Dimosthenis Giamouridis, Young Chul Kim, Zhen Tan, Tracy Guo, Wolfgang H Dillmann, Jorge Suarez, H Kirk Hammond
OBJECTIVE: To test the hypothesis that cardiac-directed expression of the cytoplasmic domains of adenylyl cyclase-6 (AC6) would have beneficial effects on the heart. BACKGROUND: Eliminating the two transmembrane domains of AC6 yields a protein with an intact catalytic domain that is disengaged from membrane-associated β-adrenergic receptor stimulation, but with enhanced propensity for intracellular interactions. METHODS: We constructed a peptide of the C1 and C2 segments of AC6 (C1C2), expressed C1C2 in an adenovirus vector and generated transgenic lines with cardiac-directed C1C2 expression, which underwent sustained isoproterenol (Iso) infusion...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#19
Ying Yang, Xiqing Rong, Xue Lv, Wenbing Jiang, Yuan Yang, Dongwu Lai, Shiming Xu, Guosheng Fu
AIM: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction. METHODS: We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28656205/role-of-pka-in-the-process-of-neonatal-cardiomyocyte-hypertrophy-induced-by-urotensin%C3%A2-ii
#20
Jianrong Xu, Qinghua Han, Hongtao Shi, Wenyuan Liu, Tingting Chu, Hao Li
The model of urotensin II (UII)-induced cardiomyocyte hypertrophy has been widely used in studies on hypertrophy. However, the molecular mechanisms responsible for UII-induced cardiomyocyte hypertrophy have not yet been fully elucidated. It has been demonstrated that cardiomyocyte hypertrophy induced by UII is associated with changes in the intracellular Ca2+ concentration. In the present study, we investigated whether the cAMP-dependent protein kinase A (PKA)‑mediated upregulation of the phosphorylation levels of phospholamban (PLN) at Ser16 contributes to UII-induced cardiomyocyte hypertrophy...
June 22, 2017: International Journal of Molecular Medicine
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