A5042676208- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Cardiac Ischemia and Reperfusion
- Metabolism, Diabetes, and Cancer
- Neuroscience and Neuropharmacology Research
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Cancer, Lipids, and Metabolism
- Autophagy in Disease and Therapy
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Cardiovascular Function and Risk Factors
- Pharmacological Effects and Assays
- Cell death mechanisms and regulation
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- ATP Synthase and ATPases Research
- Neuropeptides and Animal Physiology
- Signaling Pathways in Disease
- interferon and immune responses
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Liver Disease Diagnosis and Treatment
Peking University
2016-2025
Center for Life Sciences
2016-2025
Institute of Molecular Medicine
2012-2020
The People's Hospital of Guangxi Zhuang Autonomous Region
2013-2018
The University of Tokyo
2017
Shenyang Pharmaceutical University
2017
King Center
2016
University of Oxford
2016
Case Western Reserve University
2016
Nanjing Medical University
2016
The goal of this study was to determine whether beta(1)-adrenergic receptor (AR) and beta(2)-AR differ in regulating cardiomyocyte survival apoptosis and, if so, explore underlying mechanisms. One potential mechanism is that cardiac can activate both G(s) G(i) proteins, whereas beta(1)-AR couples only G(s). To avoid complicated crosstalk between beta-AR subtypes, we expressed or individually adult beta(1)/beta(2)-AR double knockout mouse myocytes by using adenoviral gene transfer....
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,...
Significance Baicalin is a major flavonoid component from the herbal medicine Scutellaria baicalensis that has been shown to have an antisteatosis effect. Through quantitative chemoproteomic profiling, we discovered baicalin acts as natural allosteric activator of carnitine palmitoyltransferase 1 (CPT1), rate-limiting enzyme fatty acid β-oxidation (FAO). By directly binding CPT1 and activating its activity accelerate degradation, can significantly ameliorate symptoms associated with hepatic...
Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate negative with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH.We examined the effects of HHcy on NASH progression, metabolism, autophagy dietary genetic mouse models, patients, primates. We employed (Fol) to reverse features mice cell culture.Serum Hcy...
Background: CaMKII (Ca 2+ /calmodulin-dependent kinase II) plays a central role in cardiac ischemia/reperfusion (I/R) injury—an important therapeutic target for ischemic heart disease. In the heart, CaMKII-δ is predominant isoform and further alternatively spliced into 11 variants. humans, CaMKII-δ9 CaMKII-δ3, major splice variants, inversely regulate cardiomyocyte viability with former pro-death latter pro-survival. However, it unknown whether specific inhibition of detrimental prevents I/R...
Abstract Cachexia affects 50–80% of patients with cancer and accounts for 20% cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate degree body weight loss in male female suffering from cachexia, as well clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype tumour-free mice dose-dependent manner. Furthermore, demonstrate adipose-specific...
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...
β1- and β2-adrenergic receptors (β1AR β2AR) are co-expressed in numerous tissues where they play a central role the responses of various organs to sympathetic stimulation. Although two receptor subtypes share some signaling pathways, each has been shown have specific regulatory properties. Given recent recognition that many G protein-coupled can form homo- heterodimers, present study was undertaken determine whether β1AR β2AR dimers cells and, if so, investigate potential functional...
Recombinant human MG53 protein can increase membrane repair after injury in cells and reduce pathology animal models of muscle muscular dystrophy.
Background— Ischemic heart disease is the greatest cause of death in Western countries. The deleterious effects cardiac ischemia are ameliorated by ischemic preconditioning (IPC), which transient protects against subsequent severe ischemia/reperfusion injury. IPC activates multiple signaling pathways, including reperfusion injury salvage kinase pathway (mainly PI3K-Akt-glycogen synthase kinase-3β [GSK3β] and ERK1/2) survivor activating factor enhancement involving activation JAK-STAT3 axis....
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...
Previous studies have shown that mitofusin 2 ( Mfn-2 ) (or hyperplasia suppressor gene [ HSG ]) inhibits vascular smooth muscle cell (VSMC) proliferation. Here, we demonstrate is a primary determinant of VSMC apoptosis. First, oxidative stress with H O , inhibition protein kinase C staurosporine, activation A forskolin, and serum deprivation concurrently elevate expression induce Second, overexpression also triggers apoptosis VSMCs in culture balloon-injured rat carotid arteries, thus...
An inexorable loss of terminally differentiated heart muscle cells is a crucial causal factor for failure. Here, we have provided several lines evidence to demonstrate that mitofusin-2 (Mfn-2; also called hyperplasia suppressor gene), member the mitofusin family, major determinant oxidative stress-mediated cardiomyocyte apoptosis. First, stress with H2O2 led concurrent increases in Mfn-2 expression and apoptosis cultured neonatal rat cardiomyocytes. Second, overexpression level similar...
Unrepaired cardiomyocyte membrane injury causes irreplaceable cell loss, leading to myocardial fibrosis and eventually heart failure. However, the cellular molecular mechanisms of cardiac repair are largely unknown. MG53, a newly identified striated muscle-specific protein, is involved in skeletal muscle repair. But role MG53 has not been determined.We sought investigate whether mediates cardiomyocytes and, if so, mechanism underlying MG53-mediated cardiomyocytes. Moreover, we determined...
Diabetic cardiomyopathy, which contributes to >50% diabetic death, is featured by myocardial lipid accumulation, hypertrophy, fibrosis, and cardiac dysfunction. The mechanism underlying cardiomyopathy poorly understood. Recent studies have shown that a striated muscle-specific E3 ligase Mitsugumin 53 (MG53, or TRIM72) constitutes primary causal factor of systemic insulin resistance metabolic disorders. Although it most abundantly expressed in myocardium, the biological pathological roles...
Although conventional genetic modification approaches for protein knockdown work very successfully due to the increasing use of CRISPR/Cas9, effective techniques achieving depletion in adult animals, especially large animals such as non-human primates, are lacking. Here, we report a chemical approach based on PROTACs technology that efficiently and quickly knocks down FKBP12 (12-kDa FK506-binding) globally vivo. Both intraperitoneal oral administration led rapid, robust, reversible...
Mitsugumin 53 (MG53 or TRIM72), a striated muscle-specific E3 ligase, promotes ubiquitin-dependent degradation of the insulin receptor and substrate-1 subsequently induces resistance, resulting in metabolic syndrome type 2 diabetes mellitus (T2DM). However, it is unknown how MG53 from muscle regulates systemic response energy metabolism. Increasing evidence demonstrates that secretes proteins as myokines cardiokines regulate processes. We hypothesize may act myokine/cardiokine, contributing...