keyword
https://read.qxmd.com/read/38516812/mechanisms-of-hypoxia-and-contractile-dysfunction-in-ischemia-reperfusion-in-hipsc-cardiomyocytes-an-in-silico-study
#1
JOURNAL ARTICLE
Mohamadamin Forouzandehmehr, Michelangelo Paci, Jari Hyttinen, Jussi T Koivumäki
Interconnected mechanisms of ischemia-reperfusion (I-R) has increased the interest in I-R in vitro experiments using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We developed a whole-cell computational model of hiPSC-CMs including the electromechanics, a metabolite-sensitive sarcoplasmic reticulum Ca2+-ATPase (SERCA), and an oxygen dynamics formulation to investigate I-R mechanisms. Moreover, we simulated the effect and action mechanism of Levosimendan (LEVO) that recently showed promising anti-arrhythmic effects in hiPSC-CMs in hypoxia...
March 22, 2024: Disease Models & Mechanisms
https://read.qxmd.com/read/38496584/enhanced-ca2-driven-arrhythmias-in-female-patients-with-atrial-fibrillation-insights-from-computational-modeling
#2
Xianwei Zhang, Yixuan Wu, Charlotte Smith, William E Louch, Stefano Morotti, Dobromir Dobrev, Eleonora Grandi, Haibo Ni
BACKGROUND AND AIMS: Substantial sex-based differences have been reported in atrial fibrillation (AF), with female patients experiencing worse symptoms, increased complications from drug side effects or ablation, and elevated risk of AF-related stroke and mortality. Recent studies revealed sex-specific alterations in AF-associated Ca2+ dysregulation, whereby female cardiomyocytes more frequently exhibit potentially proarrhythmic Ca2+-driven instabilities compared to male cardiomyocytes...
March 13, 2024: bioRxiv
https://read.qxmd.com/read/38473855/behavior-of-hypertrophied-right-ventricle-during-the-development-of-left-ventricular-failure-due-to-myocardial-infarction
#3
REVIEW
Naranjan S Dhalla, Karina Oliveira Mota, Carla Maria Lins de Vasconcelos, Adriana Adameova
In order to determine the behavior of the right ventricle, we have reviewed the existing literature in the area of cardiac remodeling, signal transduction pathways, subcellular mechanisms, β-adrenoreceptor-adenylyl cyclase system and myocardial catecholamine content during the development of left ventricular failure due to myocardial infarction. The right ventricle exhibited adaptive cardiac hypertrophy due to increases in different signal transduction pathways involving the activation of protein kinase C, phospholipase C and protein kinase A systems by elevated levels of vasoactive hormones such as catecholamines and angiotensin II in the circulation at early and moderate stages of heart failure...
February 23, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38466006/ca2-depletion-in-the-er-causes-store-operated-ca2-entry-via-the-trpc6-channel-in-mouse-brown-adipocytes
#4
JOURNAL ARTICLE
R Hayato, T Matsumoto, Y Higure
beta3-adrenergic activation causes Ca2+ release from the mitochondria and subsequent Ca2+ release from the endoplasmic reticulum (ER), evoking store-operated Ca2+ entry (SOCE) due to Ca2+ depletion from the ER in mouse brown adipocytes. In this study, we investigated how Ca2+ depletion from the ER elicits SOCE in mouse brown adipocytes using fluorometry of intracellular Ca2+ concentration ([Ca2+]i). The administration of cyclopiazonic acid (CPA), a reversible sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump blocker in the ER, caused an increase in [Ca2+]i...
March 11, 2024: Physiological Research
https://read.qxmd.com/read/38464201/protein-carbonylation-causes-sarcoplasmic-reticulum-ca2-overload-by-increasing-intracellular-na-level-in-ventricular-myocytes
#5
Elisa Bovo, Jaroslava Seflova, Seth L Robia, Aleksey V Zima
Diabetes is commonly associated with an elevated level of reactive carbonyl species due to alteration of glucose and fatty acid metabolism. These metabolic changes cause an abnormality in cardiac Ca 2+ regulation that can lead to cardiomyopathies. In this study, we explored how the reactive α-dicarbonyl methylglyoxal (MGO) affects Ca 2+ regulation in mouse ventricular myocytes. Analysis of intracellular Ca 2+ dynamics revealed that MGO (200 µM) increases action potential (AP)-induced Ca 2+ transients and sarcoplasmic reticulum (SR) Ca 2+ load, with a limited effect on L - type Ca 2+ channel-mediated Ca 2+ transients and SERCA - mediated Ca 2+ uptake...
March 1, 2024: Research Square
https://read.qxmd.com/read/38354857/decreased-sarcoplasmic-reticulum-phospholipids-in-human-skeletal-muscle-are-associated-with-metabolic-syndrome
#6
JOURNAL ARTICLE
Samantha E Adamson, Sangeeta Adak, Max C Petersen, Dustin Higgins, Larry D Spears, Rong Mei Zhang, Andrea Cedeno, Alexis McKee, Aswathi Kumar, Sudhir Singh, Fong-Fu Hsu, Janet B McGill, Clay F Semenkovich
Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) activity and insulin sensitivity. To determine if the presence of metabolic syndrome alters specific phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in human sarcoplasmic reticulum (SR), we compared SR phospholipid composition in skeletal muscle from sedentary subjects with metabolic syndrome and sedentary control subjects without metabolic syndrome...
February 12, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38342975/mechanisms-involved-in-the-muscle-relaxing-effects-of-stw-5-in-guinea-pig-stomach
#7
JOURNAL ARTICLE
Shady Allam, Dagmar Krüger, Klaus Michel, Katharina Schnabl, Martin Klingenspor, Michael Schemann, Anita Annaházi
INTRODUCTION: The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation. METHODS: STW 5-induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath...
February 11, 2024: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://read.qxmd.com/read/38339835/il-37-modulates-myocardial-calcium-handling-via-the-p-stat3-serca2a-axis-in-hf-related-engineered-human-heart-tissue
#8
JOURNAL ARTICLE
Dan Yin, Yong Liu, Bingqing Xue, Rui Ding, Gang Wang, Shutao Xia, Donghui Zhang
Interleukin-37 (IL-37) is a potent anti-inflammatory cytokine belonging to the IL-1 family. This study investigates the regulatory mechanism and reparative effects of IL-37 on HF-related human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) and engineered human heart tissue subjected to hypoxia and H2 O2 treatment. The contractile force and Ca2+ conduction capacity of the tissue were assessed using a stretching platform and high-resolution fluorescence imaging system. Our investigation reveals that IL-37 treatment significantly enhances cell viability, calcium transient levels, contractile force and Ca2+ conduction capacity in HF-related hiPSC-CMs and engineered human heart tissue...
February 9, 2024: Advanced Healthcare Materials
https://read.qxmd.com/read/38271051/fructose-aggravates-copper-deficiency-induced-cardiac-remodeling-by-inhibiting-serca2a
#9
JOURNAL ARTICLE
Yi Xu, Qiuxia Xu, Zhirui Zheng, Xin Jiang, Yuansen Shi, Yipu Huang, Yun Liu
OBJECTIVES: Accumulating evidence demonstrates that copper deficiency (CuD) is a risk factor for cardiovascular diseases, besides, fructose has been strongly linked to the development of cardiovascular diseases. However, how CuD or fructose causes cardiovascular diseases is not clearly delineated. The present study aims to investigate the mechanism of CuD or fructose on cardiac remodeling. METHODS: We established a model of CuD- or fructose-induced cardiac hypertrophy in 3-week-old male Sprague-Dawley (SD) rats by CuD diet supplemented with or without 30% fructose for 4 weeks...
January 25, 2024: Journal of Pharmacy and Pharmacology
https://read.qxmd.com/read/38252301/the-protective-effects-of-gallic-acid-and-sgk1-inhibitor-on-cardiac-damage-and-genes-involved-in-ca2-homeostasis-in-an-isolated-heart-model-of-ischemia-reperfusion-injury-in-rat
#10
JOURNAL ARTICLE
Faramarz Souri, Mohammad Badavi, Mahin Dianat, Ali Mard, Alireza Sarkaki, Reza Noei Razliqi
Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play a vital role in myocardial ischemia/reperfusion (I/R) injury. This enzyme may affect sarcoplasmic reticulum Ca2+ ATPase (SERCA2), ryanodine receptor (RyR2) and sodium/calcium exchanger (NCX1) during myocardial ischemia/reperfusion injury. The objective of this investigation was to analyze the effects of the combination of GSK650394 (SGK1 inhibitor) and gallic acid on the calcium ions regulation, inflammation, and cardiac dysfunction resulting from ischemia/reperfusion (I/R) injury in the heart...
January 22, 2024: Naunyn-Schmiedeberg's Archives of Pharmacology
https://read.qxmd.com/read/38243248/selective-serca2a-activator-as-a-candidate-for-chronic-heart-failure-therapy
#11
JOURNAL ARTICLE
Martina Arici, Shih-Che Hsu, Mara Ferrandi, Paolo Barassi, Carlotta Ronchi, Eleonora Torre, Andrea Luraghi, Gwo-Jyh Chang, Patrizia Ferrari, Giuseppe Bianchi, Francesco Peri, Antonio Zaza, Marcella Rocchetti
BACKGROUND: The sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) depression substantially contributes to diastolic dysfunction in heart failure (HF), suggesting that SERCA2a stimulation may be a mechanism-based HF therapy. Istaroxime is a drug endowed with both a SERCA2a stimulatory activity and a Na+ /K+ pump inhibitory activity for acute HF treatment. Its main metabolite PST3093 shows a more favorable therapeutic profile as compared to the parent drug, but it is still unsuitable for chronic usage...
January 19, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38223925/ca-2-storage-function-is-altered-in-the-sarcoplasmic-reticulum-of-skeletal-muscle-lacking-mitsugumin-23
#12
JOURNAL ARTICLE
Daiki Watanabe, Miyuki Nishi, Feng Liu, Yuhan Bian, Hiroshi Takeshima
Mitsugumin 23 (MG23) has been identified as a ball-shaped cation channel in the sarcoplasmic reticulum (SR) but its physiological role remains unclear. This study aimed to examine the contribution of MG23 to Ca2+ storage function in skeletal muscle by using Mg23 -knockout ( Mg23 -/- ) mice. There was no difference in the isometric specific force of the extensor digitorum longus (EDL) and soleus (SOL) muscles between Mg23 -/- and wild-type (Wt) mice. In Mg23 -/- mice, the calsequestrin 2 content in the EDL muscle and SR Ca2+ -ATPase 2 content in the SOL were increased...
January 15, 2024: American Journal of Physiology. Cell Physiology
https://read.qxmd.com/read/38222469/mechanisms-for-cardiac-calcium-pump-activation-by-its-substrate-and-a-synthetic-allosteric-modulator-using-fluorescence-lifetime-imaging
#13
JOURNAL ARTICLE
Jaroslava Šeflová, Carlos Cruz-Cortés, Guadalupe Guerrero-Serna, Seth L Robia, L Michel Espinoza-Fonseca
The discovery of allosteric modulators is an emerging paradigm in drug discovery, and signal transduction is a subtle and dynamic process that is challenging to characterize. We developed a time-correlated single photon-counting imaging approach to investigate the structural mechanisms for small-molecule activation of the cardiac sarcoplasmic reticulum Ca2+ -ATPase, a pharmacologically important pump that transports Ca2+ at the expense of adenosine triphosphate (ATP) hydrolysis. We first tested whether the dissociation of sarcoplasmic reticulum Ca2+ -ATPase from its regulatory protein phospholamban is required for small-molecule activation...
January 2024: PNAS Nexus
https://read.qxmd.com/read/38217607/serca1-overexpression-in-skeletal-muscle-attenuates-muscle-atrophy-and-improves-motor-function-in-a-mouse-model-of-als
#14
JOURNAL ARTICLE
Davi A G Mázala, Dapeng Chen, Eva R Chin
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of muscle mass and muscle function. Previous work from our lab demonstrated that skeletal muscles from a mouse model of ALS show elevated intracellular calcium (Ca2 +) levels and heightened endoplasmic reticulum (ER) stress. OBJECTIVE: To investigate whether overexpression of sarcoplasmic reticulum (SR) Ca2 + ATPase 1 (SERCA1) in skeletal muscle would improve intracellular Ca2 + handling, attenuate ER stress, and improve motor function ALS transgenic mice...
January 10, 2024: Journal of Neuromuscular Diseases
https://read.qxmd.com/read/38166470/zbtb20-regulates-serca2a-activity-and-myocardial-contractility-through-phospholamban
#15
JOURNAL ARTICLE
An-Jing Ren, Chunchun Wei, Ya-Jin Liu, Mengna Liu, Ping Wang, Juan Fan, Kai Wang, Sha Zhang, Zhenbang Qin, Qiu-Xiao Ren, Yanjun Zheng, Yu-Xia Chen, Zhifang Xie, Ling Gao, Yi Zhu, Youyi Zhang, Huang-Tian Yang, Weiping J Zhang
BACKGROUND: Intracellular Ca2+ cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase 2a) is responsible for the sequestration of cytosolic Ca2+ into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear. METHODS: Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20 flox mice with Myh6 -Cre mice...
January 3, 2024: Circulation Research
https://read.qxmd.com/read/38163553/serca2-dysfunction-triggers-hypertension-by-interrupting-mitochondrial-homeostasis-and-provoking-oxidative-stress
#16
JOURNAL ARTICLE
Yaping Wang, Min Wang, Hang Su, Jiarou Song, Minghua Ren, Pingping Hu, Gang Liu, Xiaoyong Tong
BACKGROUND AND AIM: Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is critical in maintaining Ca2+ homeostasis. The cysteine 674 (C674) is the key redox regulatory cysteine in regulating SERCA2 activity, which is irreversibly oxidized in the renal cortex of hypertensive mice. We have reported that the substitution of C674 by serine causes SERCA2 dysfunction and increases blood pressure by induction of endoplasmic reticulum stress (ERS). This study is to explore whether the dysfunction of SERCA2 causes hypertension by interrupting mitochondrial homeostasis and inducing oxidative stress...
December 30, 2023: Free Radical Biology & Medicine
https://read.qxmd.com/read/38152112/calcium-signaling-mediates-proliferation-of-the-precursor-cells-that-give-rise-to-the-ciliated-left-right-organizer-in-the-zebrafish-embryo
#17
JOURNAL ARTICLE
Osama Abdel-Razek, Amanda Marzouk, Madison MacKinnon, Edward T Guy, Sonny A Pohar, Emily Zhushma, Junjie Liu, Isabel Sia, Jason J Gokey, Hwee Goon Tay, Jeffrey D Amack
Several of our internal organs, including heart, lungs, stomach, and spleen, develop asymmetrically along the left-right (LR) body axis. Errors in establishing LR asymmetry, or laterality, of internal organs during early embryonic development can result in birth defects. In several vertebrates-including humans, mice, frogs, and fish-cilia play a central role in establishing organ laterality. Motile cilia in a transient embryonic structure called the "left-right organizer" (LRO) generate a directional fluid flow that has been proposed to be detected by mechanosensory cilia to trigger asymmetric signaling pathways that orient the LR axis...
2023: Frontiers in Molecular Biosciences
https://read.qxmd.com/read/38099489/remodelling-of-camp-dynamics-within-the-serca2a-microdomain-in-heart-failure-with-preserved-ejection-fraction-caused-by-obesity-and-type-2-diabetes
#18
JOURNAL ARTICLE
Ping Lai, Susanne S Hille, Hariharan Subramanian, Robert Weigman, Pia Roser, Oliver J Müller, Viacheslav O Nikolaev, Kirstie A De Jong
AIMS: Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a) which forms a functional cardiomyocyte (CM) microdomain where 3',5'-cyclic adenosine monophosphate (cAMP) produced upon β-adrenoceptor (β-AR) stimulation leads to phospholamban (PLN) phosphorylation and facilitated Ca2+ reuptake...
December 14, 2023: Cardiovascular Research
https://read.qxmd.com/read/38082185/mandatory-role-of-endoplasmic-reticulum-and-its-pentose-phosphate-shunt-in-the-myocardial-defense-mechanisms-against-the-redox-stress-induced-by-anthracyclines
#19
JOURNAL ARTICLE
Gianmario Sambuceti, Vanessa Cossu, Francesca Vitale, Eva Bianconi, Sonia Carta, Consuelo Venturi, Sabrina Chiesa, Francesco Lanfranchi, Laura Emionite, Sebastiano Carlone, Luca Sofia, Francesca D'Amico, Tania Di Raimondo, Silvia Chiola, Anna Maria Orengo, Silvia Morbelli, Pietro Ameri, Matteo Bauckneht, Cecilia Marini
Anthracyclines' cardiotoxicity involves an accelerated generation of reactive oxygen species. This oxidative damage has been found to accelerate the expression of hexose-6P-dehydrogenase (H6PD), that channels glucose-6-phosphate (G6P) through the pentose phosphate pathway (PPP) confined within the endoplasmic/sarcoplasmic reticulum (SR). To verify the role of SR-PPP in the defense mechanisms activated by doxorubicin (DXR) in cardiomyocytes, we tested the effect of this drug in H6PD knockout mice (H6PD-/- )...
December 12, 2023: Molecular and Cellular Biochemistry
https://read.qxmd.com/read/38048655/in-vivo-heat-production-dynamics-during-a-contraction-relaxation-cycle-in-rat-single-skeletal-muscle-fibers
#20
JOURNAL ARTICLE
Ayaka Tabuchi, Yoshinori Tanaka, Hiroshi Horikawa, Takuto Tazawa, David C Poole, Yutaka Kano
Skeletal muscle generates heat via contraction-dependent (shivering) and independent (nonshivering) mechanisms. While this thermogenic capacity of skeletal muscle undoubtedly contributes to the body temperature homeostasis of animals and impacts various cellular functions, the intracellular temperature and its dynamics in skeletal muscle in vivo remain elusive. We aimed to determine the intracellular temperature and its changes within skeletal muscle in vivo during contraction and following relaxation. In addition, we tested the hypothesis that sarcoplasmic reticulum Ca2+ ATPase (SERCA) generates heat and increases the myocyte temperature during a transitory Ca2+ -induced contraction-relaxation cycle...
November 30, 2023: Journal of Thermal Biology
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