A5066990063- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Adipose Tissue and Metabolism
- Pluripotent Stem Cells Research
- Ion Channels and Receptors
- RNA Research and Splicing
- Photoreceptor and optogenetics research
- Cardiomyopathy and Myosin Studies
- Wireless Signal Modulation Classification
- Physiological and biochemical adaptations
- MicroRNA in disease regulation
- Signaling Pathways in Disease
- Connexins and lens biology
- Chemical and Physical Properties in Aqueous Solutions
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Extraction and Separation Processes
- Electrochemical Analysis and Applications
- Calcium Carbonate Crystallization and Inhibition
- Cardiac Ischemia and Reperfusion
Peking University
2016-2025
Chongqing Cancer Hospital
2017-2025
Chongqing University
2018-2025
Beihang University
2025
Chinese Institute for Brain Research
2021-2024
Center for Life Sciences
2013-2024
Peking University Sixth Hospital
2024
Wuhan University
2024
Renmin Hospital of Wuhan University
2024
Tianjin University of Science and Technology
2011-2024
beta(1)-adrenergic receptor (beta(1)AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from change of gene expression control metabolism, muscle contraction, and cell apoptosis. Here we show that sustained beta(1)AR promotes cardiac myocyte apoptosis by activation Ca(2+)/calmodulin II (CaMKII), independently PKA signaling. beta(1)AR-induced is resistant inhibition a specific peptide inhibitor, PKI14-22, or an inactive cAMP analogue,...
Abstract The beating heart possesses the intrinsic ability to adapt cardiac output changes in mechanical load. century-old Frank–Starling law and Anrep effect have documented that stretching during diastolic filling increases its contractile force. However, molecular mechanotransduction mechanism impact on health disease remain elusive. Here we show mechanically activated Piezo1 channel converts stretch of cardiomyocytes into Ca 2+ reactive oxygen species (ROS) signaling, which critically...
β1-adrenergic receptor (β1AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from change of gene expression control metabolism, muscle contraction, and cell apoptosis. Here we show that sustained β1AR promotes cardiac myocyte apoptosis by activation Ca2+/calmodulin II (CaMKII), independently PKA signaling. β1AR-induced is resistant inhibition a specific peptide inhibitor, PKI14-22, or an inactive cAMP analogue, Rp-8-CPT-cAMPS. In...
Rapid development of transgenic and gene-targeted mice acute genetic manipulation via gene transfer vector systems have provided powerful tools for cardiovascular research. To facilitate the phenotyping genetically engineered murine models at cellular subcellular levels to implement techniques in single mouse cardiomyocytes, we modified improved current enzymatic methods isolate a high yield high-quality adult myocytes (5.3 +/- 0.5 x 10(5) cells/left ventricle, 83.8 2.5% rod shaped). We also...
p38 Mitogen-activated protein kinase (MAPK) is one of the most ancient signaling molecules and involved in multiple cellular processes, including cell proliferation, growth, death. In heart, enhanced activation MAPK associated with ischemia/reperfusion injury onset heart failure. present study, we investigated function regulating cardiac contractility its underlying mechanisms. cultured adult rat cardiomyocytes, by adenoviral gene transfer an activated mutant upstream kinase, MKK3bE, led to...
A tenet of beta1-adrenergic receptor (beta1AR) signaling is that stimulation the activates adenylate cyclase-cAMP-protein kinase (PKA) pathway, resulting in positive inotropic and relaxant effects heart. However, recent studies have suggested involvement Ca2+/calmodulin-dependent protein II (CaMKII) beta1AR-stimulated cardiac apoptosis. In this study, we determined roles CaMKII PKA sustained versus short-term beta1AR modulation excitation-contraction (E-C) coupling myocytes. Short-term...
FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found marked reduction of expression in the livers db/db high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression markedly attenuated hyperglycemia, insulin resistance, fatty liver with increased Akt (pAkt) signaling repressed gluconeogenesis lipogenesis those contrast, small interfering RNA (siRNA)-mediated knockdown hepatic resulted hyperglycemia reduced pAkt...
Abstract Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about contributions of microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data mouse hearts at multiple stages, we construct cellular interactomes regulatory signaling networks. Here report switching fibroblast subtypes from a neonatal adult state this drives Molecular functional cardiomyocytes human embryonic stem cell-derived are considerably...
Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy reducing cardiac I/R injury. CaMKII (Ca2+/calmodulin-dependent kinase II) plays a pivotal role in pathogenesis severe conditions, including Pharmacological inhibition strategy protection against myocardial damage diseases. To date, drug targeting clinical disease. Furthermore, at...
Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular signals and cellular activities in living organisms. Current GECIs face the challenge suboptimal peak signal-to-baseline ratio (SBR) with limited resolution reporting subtle transients. We report herein development a suite sensors, designated NEMO, fast kinetics wide dynamic ranges (>100-fold). NEMO Ca2+ transients SBRs around 20-fold larger than top-of-the-range GCaMP6 series....
Abstract —To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by β-adrenergic receptor (β-AR) stimulation, we examined local Ca 2+ release function, ie, spikes at individual transverse tubule–sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique for flux measurement. β-AR stimulation norepinephrine plus an α 1 -adrenergic blocker, prazosin, increased amplitude SR (J ), its running...
Intracellular Ca 2+ release in many types of cells is mediated by ryanodine receptor channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays the endoplasmic/sarcoplasmic reticulum. However, situ operating mechanism RyRC array unknown. Here, we found elementary events, sparks from individual rat ventricular myocytes, exhibit quantized flux. Analysis quantal property provided a view unitary current and gating kinetics intact revealed spark activation involves dynamic...
Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as major mechanism underlying defective E-C However, regulatory JP2 remains unknown.To determine whether microRNAs regulate expression.Bioinformatic analysis predicted 2 potential binding sites miR-24 in 3'-untranslated regions mRNA. Luciferase assays confirmed that suppressed...
Chronic heart failure is a complex clinical syndrome with impaired myocardial contractility. In failing cardiomyocytes, decreased signalling efficiency between the L-type Ca2+ channels (LCCs) in plasma membrane (including transverse tubules, TTs) and ryanodine receptors (RyRs) sarcoplasmic reticulum (SR) underlies defective excitation–contraction (E–C) coupling. It therefore intriguing to know how LCC–RyR apparatus remodelled human failure. Stereological analysis of transmission electron...
Rationale: During the transition from compensated hypertrophy to heart failure, signaling between L-type Ca 2+ channels in cell membrane/T-tubules and ryanodine receptors sarcoplasmic reticulum becomes defective, partially because of decreased expression a T-tubule–sarcoplasmic anchoring protein, junctophilin-2. MicroRNA (miR)-24, junctophilin-2 suppressing miR, is upregulated hypertrophied failing cardiomyocytes. Objective: To test whether miR-24 suppression can protect structural...
In the heart, glycosylation is involved in a variety of physiological and pathological processes. Cardiac dynamically regulated, which remains challenging to monitor vivo. Here we describe chemical approach for analyzing dynamic cardiac glycome by metabolically labeling glycans with azidosugars living rats. The azides, serving as reporter, are chemoselectively conjugated fluorophores using copper-free click chemistry glycan imaging; derivatizing azides affinity tags allows enrichment...
Rationale: In cardiac dyads, junctional Ca 2+ directly controls the gating of ryanodine receptors (RyRs), and is itself dominated by RyR-mediated release from sarcoplasmic reticulum. Existing probes do not report such local signals because probe diffusion, so a junction-targeted sensor should reveal new information on excitation–contraction coupling its modification in disease states. Objective: To investigate signaling nanoscopic space dyads targeting sensitive biosensor (GCaMP6f) to space....
Abstract Mesenchymal stem cells (MSCs) are multipotential residing in the bone marrow. Several studies have shown that mechanical stimulation modulates MSC differentiation through mobilization of second messengers, but mechanism mechanotransduction remains poorly understood. In this study, using fluorescence and laser confocal microcopy as well patch-clamp techniques, we identified transient receptor potential melastatin type 7 (TRPM7) channel key involved marrow MSCs. TRPM7 knockdown...
Precise genetic mutation of model animals is highly valuable for functional investigation human mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-induced homology-directed repair (HDR) usually used precise mutation, being limited by the relatively low efficiency compared with that non-homologous end joining (NHEJ). Although inhibition NHEJ was shown to enhance HDR-derived in this work, without NHEJ, we first generated gene-modified pigs...