keyword
https://read.qxmd.com/read/38534320/phosphodiesterases-4b-and-4d-differentially-regulate-camp-signaling-in-calcium-handling-microdomains-of-mouse-hearts
#1
JOURNAL ARTICLE
Axel E Kraft, Nadja I Bork, Hariharan Subramanian, Nikoleta Pavlaki, Antonio V Failla, Bernd Zobiak, Marco Conti, Viacheslav O Nikolaev
The ubiquitous second messenger 3',5'-cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling (ECC) by signaling in discrete subcellular microdomains. Phosphodiesterase subfamilies 4B and 4D are critically involved in the regulation of cAMP signaling in mammalian cardiomyocytes. Alterations of PDE4 activity in human hearts has been shown to result in arrhythmias and heart failure. Here, we sought to systematically investigate specific roles of PDE4B and PDE4D in the regulation of cAMP dynamics in three distinct subcellular microdomains, one of them located at the caveolin-rich plasma membrane which harbors the L-type calcium channels (LTCCs), as well as at two sarco/endoplasmic reticulum (SR) microdomains centered around SR Ca2+ -ATPase (SERCA2a) and cardiac ryanodine receptor type 2 (RyR2)...
March 8, 2024: Cells
https://read.qxmd.com/read/38531956/darier-disease-is-associated-with-neurodegenerative-disorders-and-epilepsy
#2
JOURNAL ARTICLE
Philip Curman, William Jebril, Henrik Larsson, Etty Bachar-Wikstrom, Martin Cederlöf, Jakob D Wikstrom
Darier disease (DD) is a rare monogenetic skin disorder with limited data on its potential association with neurological disorders. This study aimed to investigate the association between DD and neurological disorders, specifically Parkinson's disease, dementias, and epilepsy. Using Swedish national registers in a period spanning between 1977 and 2013, 935 individuals with DD were compared with up to 100 comparison individuals each, randomly selected from the general population based on birth year, sex, and county of residence at the time of the first diagnosis of DD...
March 26, 2024: Scientific Reports
https://read.qxmd.com/read/38531438/capsaicin-induces-atp-dependent-thermogenesis-via-the-activation-of-trpv1-%C3%AE-3-ar-%C3%AE-1-ar-in-3t3-l1-adipocytes-and-mouse-model
#3
JOURNAL ARTICLE
Abdillah Alfin Mohammad, Jong Won Yun
Capsaicin (CAP) is a natural bioactive compound in chili pepper that activates the transient receptor potential vanilloid subfamily 1 (TRPV1) and is known to stimulate uncoupling protein 1 (UCP1)-dependent thermogenesis. However, its effect on ATP-dependent thermogenesis remains unknown. In this study, we employed qRT-PCR, immunoblot, staining method, and assay kit to investigate the role of CAP on ATP-dependent thermogenesis and its modulatory roles on the TRPV1, β3-adrenergic receptor (β3-AR), and α1-AR using in vitro and in vivo models...
March 24, 2024: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/38516812/mechanisms-of-hypoxia-and-contractile-dysfunction-in-ischemia-reperfusion-in-hipsc-cardiomyocytes-an-in-silico-study
#4
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/38514666/trimethylamine-n-oxide-impairs-%C3%AE-cell-function-and-glucose-tolerance
#5
JOURNAL ARTICLE
Lijuan Kong, Qijin Zhao, Xiaojing Jiang, Jinping Hu, Qian Jiang, Li Sheng, Xiaohong Peng, Shusen Wang, Yibing Chen, Yanjun Wan, Shaocong Hou, Xingfeng Liu, Chunxiao Ma, Yan Li, Li Quan, Liangyi Chen, Bing Cui, Pingping Li
β-Cell dysfunction and β-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, β-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on β-cell function in vitro and in vivo...
March 21, 2024: Nature Communications
https://read.qxmd.com/read/38507587/the-ailing-%C3%AE-cell-in-diabetes-insights-from-a-trip-to-the-er-the-2023-outstanding-scientific-achievement-award-lecture
#6
JOURNAL ARTICLE
Carmella Evans-Molina
The synthesis, processing, and secretion of insulin by the pancreatic β-cell is key for the maintenance of systemic metabolic homeostasis, and loss or dysfunction of β-cells underlies the development of both type 1 diabetes (T1D) and type 2 diabetes (T2D). Work in the Evans-Molina laboratory over the past 15 years has pioneered the idea that regulation of calcium dynamics is critical to β-cell biology and diabetes pathophysiology. In this article, I will share three vignettes from the laboratory that demonstrate our bench-to-bedside approach to determining mechanisms of β-cell stress that could improve therapeutic options and outcomes for individuals living with diabetes...
April 1, 2024: Diabetes
https://read.qxmd.com/read/38500692/qifu-yixin-formula-improves-heart-failure-by-enhancing-%C3%AE-arrestin2-mediated-the-sumoylation-of-serca2a
#7
JOURNAL ARTICLE
Xinting Wang, Jiahui Yang, Cheng Lu, Yinqin Hu, Zhaohui Xu, Qiqi Wan, Meng Zhang, Tianyun Shi, Zhirui Liu, Yongming Liu
PURPOSE: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting β-arrestin2 (β-arr2)-mediated SERCA2a SUMOylation. MATERIALS AND METHODS: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. β-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro...
2024: Drug Design, Development and Therapy
https://read.qxmd.com/read/38493225/a-novel-role-for-phospholamban-in-the-thalamic-reticular-nucleus
#8
JOURNAL ARTICLE
Benjamin Klocke, Aikaterini Britzolaki, Joseph Saurine, Hayden Ott, Kylie Krone, Kiara Bahamonde, Connor Thelen, Christos Tzimas, Despina Sanoudou, Evangelia G Kranias, Pothitos M Pitychoutis
The thalamic reticular nucleus (TRN) is a brain region that influences vital neurobehavioral processes, including executive functioning and the generation of sleep rhythms. TRN dysfunction underlies hyperactivity, attention deficits, and sleep disturbances observed across various neurodevelopmental disorders. A specialized sarco-endoplasmic reticulum calcium (Ca2+ ) ATPase 2 (SERCA2)-dependent Ca2+  signaling network operates in the dendrites of TRN neurons to regulate their bursting activity. Phospholamban (PLN) is a prominent regulator of SERCA2 with an established role in myocardial Ca2 + -cycling...
March 16, 2024: Scientific Reports
https://read.qxmd.com/read/38488467/involvement-of-nucleus-accumbens-serca2b-in-methamphetamine-induced-conditioned-place-preference
#9
JOURNAL ARTICLE
Yujing Wang, Fan Duan, Junda Li, Xiangyu Li, Lingling Xia, Wei Zhao, Ze Wang, Xun Song, Juan Chen, Jingjing Wang, Yue Wang, Jing Zhang, Xiaochu Zhang, Dongliang Jiao
Methamphetamine (METH) is a highly addictive psycho-stimulant that induces addictive behaviour by stimulating increased dopamine release in the nucleus accumbens (NAc). The sarco/endoplasmic reticulum calcium ion transport ATPases (SERCA or ATP2A) is a calcium ion (Ca2+) pump in the endoplasmic reticulum (ER) membrane. SERCA2b is a SERCA subtype mainly distributed in the central nervous system. This study used conditioned place preference (CPP), a translational drug reward model, to observe the effects of SERCA and SERCA2b on METH-CPP in mice...
March 2024: Addiction Biology
https://read.qxmd.com/read/38482846/terpenes-and-terpenoids-conjugated-with-bodipys-an-overview-of-biological-and-chemical-properties
#10
REVIEW
Jarmila Stanková, Michal Jurášek, Marián Hajdúch, Petr Džubák
Advancements in small-molecule research have created the need for sensitive techniques to accurately study biological processes in living systems. Fluorescent-labeled probes have become indispensable tools, particularly those that use boron-dipyrromethene (BODIPY) dyes. Terpenes and terpenoids are organic compounds found in nature that offer diverse biological activities, and BODIPY-based probes play a crucial role in studying these compounds. Monoterpene-BODIPY conjugates have exhibited potential for staining bacterial and fungal cells...
March 14, 2024: Journal of Natural Products
https://read.qxmd.com/read/38478641/exacerbation-of-darier-disease-with-lithium-therapy
#11
JOURNAL ARTICLE
Shant Tamazian, Cory L Simpson
Darier disease is an autosomal dominant blistering disorder linked to mutation of the endoplasmic reticulum calcium pump, SERCA2, which compromises keratinocyte adhesion and differentiation. Beyond the typical keratotic and eroded skin lesions, patients with Darier disease often present with psychiatric co-morbidities. Herein, we present a biopsy-confirmed case of Darier disease in a patient with bipolar disorder, whose cutaneous disease dramatically worsened upon initiation of lithium therapy. In consultation with the patient's psychiatrist, lithium was tapered, leading to rapid improvement in her skin...
October 15, 2023: Dermatology Online Journal
https://read.qxmd.com/read/38466006/ca2-depletion-in-the-er-causes-store-operated-ca2-entry-via-the-trpc6-channel-in-mouse-brown-adipocytes
#12
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
#13
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/38462228/plasma-membrane-calcium-atpase-powered-by-glycolysis-is-the-main-mechanism-for-calcium-clearance-in-the-hippocampal-pyramidal-neuron
#14
JOURNAL ARTICLE
Vitor S Alves, Fernando A Oliveira
AIMS: This study sought to elucidate the primary ATP-dependent mechanisms involved in clearing cytosolic Ca2+ in neurons and determine the predominant ATP-generating pathway-glycolysis or tricarboxylic acid cycle/oxidative phosphorylation (TCA/OxPhos)-associated with these mechanisms in hippocampal pyramidal neurons. MAIN METHODS: Our investigation involved evaluating basal Ca2+ levels and analyzing the kinetic characteristics of evoked neuronal Ca2+ transients after selectively combined the inhibition/blockade of key ATP-dependent mechanisms with the suppression of either TCA/OxPhos or glycolytic ATP sources...
March 8, 2024: Life Sciences
https://read.qxmd.com/read/38458821/corrigendum-to-chronic-melatonin-treatment-improves-obesity-by-inducing-uncoupling-of-skeletal-muscle-serca-sln-mediated-by-camkii-ampk-pgc1%C3%AE-pathway-and-mitochondrial-biogenesis-in-female-and-male-z%C3%A3-cker-diabetic-fatty-rats-biomed-pharmacother-172-2024-116314
#15
D Salagre, M Navarro-Alarcón, M Villalón-Mir, B Alcázar-Navarrete, G Gómez-Moreno, F Tamimi, A Agil
No abstract text is available yet for this article.
March 7, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38455159/ginseng-in-white-and-red-processed-forms-ginsenosides-and-cardiac-side-effects
#16
JOURNAL ARTICLE
Jiexin Zhou, Jiarui Zhang, Pu Jing, Yu Lan, Xiaonian Cao, Huafang Feng, Xiaogang Liu, Qingqing Liu
Ginseng ( Panax ginseng Meyer) has long been consumed as a medicinal or functional food in East Asia. It is available as dried white ginseng (WG) and steamed red ginseng (RG), which might differ in ginsenoside profiles. We compared ginsenoside types of RG and WG using UPLC-MS/MS and evaluated how they biologically affected heart of healthy rats by recording electrocardiography, measuring biochemical indicators, analyzing cardiac tissue slides, and Ca2+ signaling pathways. About 25 and 29 ginsenosides were detected in WG and RG, respectively, and the total ginsenoside content of RG contained was nearly 1...
March 2024: Food Science & Nutrition
https://read.qxmd.com/read/38438822/protective-effect-of-serca2a-sumoylation-by-sumo-1-on-diabetes-induced-atherosclerosis-and-aortic-vascular-injury
#17
JOURNAL ARTICLE
Jinlin Liu, Shifang Xu, Bin Gao, Meng Yuan, Li Zhong, Rui Guo
Diabetes is a major risk factor for cardiovascular disease. However, the exact mechanism by which diabetes contributes to vascular damage is not fully understood. The aim of this study was to investigate the role of SUMO-1 mediated SERCA2a SUMOylation in the development of atherosclerotic vascular injury associated with diabetes mellitus. ApoE-/- mice were treated with streptozotocin (STZ) injection combined with high-fat feeding to simulate diabetic atherosclerosis and vascular injury. Human aortic vascular smooth muscle cells (HAVSMCs) were treated with high glucose (HG, 33...
March 5, 2024: Molecular and Cellular Biochemistry
https://read.qxmd.com/read/38429580/author-correction-toll-like-receptor-9-protects-non-immune-cells-from-stress-by-modulating-mitochondrial-atp-synthesis-through-the-inhibition-of-serca2
#18
Yasunori Shintani, Hannes Ca Drexler, Hidetaka Kioka, Cesare Mn Terracciano, Steven R Coppen, Hiromi Imamura, Masaharu Akao, Junichi Nakai, Ann P Wheeler, Shuichiro Higo, Hiroyuki Nakayama, Seiji Takashima, Kenta Yashiro, Ken Suzuki
No abstract text is available yet for this article.
March 1, 2024: EMBO Reports
https://read.qxmd.com/read/38421408/pthrp-attenuates-spontaneous-contractions-in-detrusor-smooth-muscle-of-the-rat-bladder-by-activating-spontaneous-transient-outward-potassium-currents
#19
JOURNAL ARTICLE
Wataru Kudo, Hikaru Hashitani
Parathyroid hormone-related protein (PTHrP) released from detrusor smooth muscle (DSM) cells upon bladder distension attenuates spontaneous phasic contractions (SPCs) in DSM and associated afferent firing to facilitate urine storage. Here, we investigate the mechanisms underlying PTHrP-induced inhibition of SPCs, focusing on large-conductance Ca2+ -activated K+ channels (BK channels) that play a central role in stabilizing DSM excitability. Perforated patch-clamp techniques were applied to DSM cells of the rat bladder dispersed using collagenase...
February 29, 2024: Pflügers Archiv: European Journal of Physiology
https://read.qxmd.com/read/38417695/metallothionein-alleviates-glutathione-depletion-induced-oxidative-cardiomyopathy-through-cisd1-dependent-regulation-of-ferroptosis-in-murine-hearts
#20
JOURNAL ARTICLE
Feng-Juan Li, Shouzhi Fu, Hua Ye, Yi-Han Hu, Jianxin Chen, Jamie R Privratsky, Wei Yu, Feng Dong, Russel J Reiter, Maolong Dong, Jun Guo, Jun Ren
This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. WT and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM in drinking water) for 14 days prior to assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity, intracellular Ca2+ handling, sarcoplasmic reticulum Ca2+ reuptake, loss of mitochondrial integrity (mitochondrial swelling, loss of aconitase activity), mitochondrial energy deficit, carbonyl damage, lipid peroxidation, ferroptosis and apoptosis...
February 26, 2024: American Journal of Pathology
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