A5091830338- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Cellular transport and secretion
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Metabolism, Diabetes, and Cancer
- Neuropeptides and Animal Physiology
- Cancer-related molecular mechanisms research
- Anesthesia and Neurotoxicity Research
- Circular RNAs in diseases
- Intensive Care Unit Cognitive Disorders
- Diabetes Treatment and Management
- Ion Transport and Channel Regulation
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion Channels and Receptors
- Calcium signaling and nucleotide metabolism
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Estrogen and related hormone effects
- Nuclear Receptors and Signaling
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
Hainan University
2025
Augusta University
2019-2024
University of Chinese Academy of Sciences
2009-2024
Shanghai Institute of Materia Medica
2015-2024
Chinese Academy of Sciences
2015-2024
Wuhan University
2016-2023
Zhongnan Hospital of Wuhan University
2016-2023
Ansteel (China)
2022-2023
Chinese PLA General Hospital
2022
Nantong University
2021-2022
Although the actin cytoskeleton has been implicated in vesicle trafficking, docking and fusion, its site of action relation to Ca(2+)-mediated activation fusion machinery have not elucidated. In this study, we examined role filaments regulated exocytosis by introducing highly specific monomer-binding proteins, beta-thymosins or a gelsolin fragment, into streptolysin O-permeabilized pancreatic acinar cells. These proteins had stimulatory inhibitory effects. Low concentrations elicited rapid...
In polarized epithelial cells [Ca<sup>2+</sup>] <sub>i</sub> waves are initiated in discrete regions and propagate through the cytosol. The structural basis for these compartmentalized coordinated events not well understood. present study we used a combination of imaging at high temporal resolution, recording Ca<sup>2+</sup>-activated Cl<sup>−</sup> current, immunolocalization by confocal microscopy to correlation between initiation propagation localization Ca<sup>2+</sup> release channels...
Regulators of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Gα subunits, thereby attenuating signaling. RGS4 is a GTPase-activating for G<sub>i</sub>and G<sub>q</sub> class α subunits. In the present study, we used knockouts genes in mice to evaluate potency and selectivity modulating Ca<sup>2+</sup> transduced different G<sub>q</sub>-coupled receptors. inhibited phospholipase C activity receptor-selective manner both permeabilized cells dialyzed with through patch pipette....
Regulators of heterotrimeric G protein signaling (RGS) proteins are GTPase-activating (GAPs) that accelerate GTP hydrolysis by G<sub>q</sub> and G<sub>i</sub> α subunits, thus attenuating signaling. Mechanisms provide more precise regulatory specificity have been elusive. We report here an N-terminal domain RGS4 discriminated among receptor complexes coupled via G<sub>q</sub>. Accordingly, deletion the eliminated selectivity reduced potency 10<sup>4</sup>-fold. Receptor inhibition were...
The mechanism of activation the agonist-stimulated Ca2+ entry pathway in plasma membrane is not known. To determine role nitric-oxide synthase (NOS) and cGMP regulation this pathway, we used intact streptolysin O (SLO)-permeable pancreatic acini measured relationship between release from internal stores, NO metabolic generation cGMP, entry. We found that agonist- or thapsigargin (Tg)-activated inhibited by L-NA, a specific inhibitor NOS, LY83583, an guanylyl cyclase. Inhibition inhibition...
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways thus an attractive therapeutic target for diabetes obesity. Starting with high micromolar lead compound, structure-based optimization novel PTP1B inhibitors by extension molecule from enzyme active site into second phosphotyrosine binding described. Medicinal chemistry, guided X-ray complex structure molecular modeling, has yielded low nanomolar in efficient manner. Compounds this...
The present study was aimed at localization of plasma membrane (PMCA) and intracellular (SERCA) Ca<sup>2+</sup>pumps characterizing their role in initiation propagation Ca<sup>2+</sup> waves. Specific polarized expression pumps observed all epithelial cells examined. Immunolocalization revealed PMCA both the basolateral luminal membranes cell types. SERCA2a appeared to be expressed pole, whereas SERCA2b basal pole nuclear envelope pancreatic acini. Interestingly, found submandibular salivary...
Neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD). Accumulated evidence indicates that cannabinoid receptor type 2 (CB2R) can mediate anti-inflammatory and immunomodulatory effects part by controlling microglial activity. However, the impact of CB2R on cognition has not been investigated. We hypothesized is involved surgery-induced impairment adult mice.Adult C57BL/6 mice were subjected to intramedullary fixation surgery for tibial fracture under isoflurane...
Significance Rett syndrome is the most common intellectual disability in women after Down (1:10,000 incidence). Different mouse models of and autism exhibit deficits synaptic plasticity, including impaired long-term potentiation (LTP) mice lacking methyl-CpG-binding protein 2 (MeCP2); however, bases this deficit remain unclear. Using a combination electrophysiology, time-lapse imaging, cell biology, biochemistry, we provide direct evidence that naïve hippocampal synapses have all hallmarks...
The naturally occurring phospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have recently emerged as bioactive compounds that exert mitogenic effects in many cell types, including osteoblasts. In the current study, we examined ability of each these to influence osteoblast survival. Using terminal deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling DNA fragmentation assays, found both LPA S1P dose-dependently inhibited (by at least 50%...
IGF-I is an endocrine and paracrine regulator of skeletal homeostasis, principally by virtue its anabolic effects on osteoblastic cells. In the current study, we examined intracellular signaling pathways which promotes proliferation survival in SaOS-2 human Inhibition each phosphatidylinositol-3 kinase (PI-3 kinase), p42/44 MAPK, p70s6 partially inhibited ability to stimulate osteoblast survival. Because activation downstream both PI-3 MAPK osteoblasts treated with IGF-I, this ribosomal...
Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is potentiated by cAMP-elevating agents, such as the incretin hormone glucagon-like peptide-1 (GLP-1), and cAMP exerts its secretagogue action activating both protein kinase A (PKA) cAMP-regulated guanine nucleotide exchange factor designated Epac2. Although prior studies of mouse islets demonstrated that Epac2 acts via Rap1 GTPase to potentiate GSIS, it not understood which downstream targets promote exocytosis insulin....
Calcium can be mobilized in pancreatic β-cells via a mechanism of Ca(2+)-induced Ca(2+) release (CICR), and cAMP-elevating agents such as exendin-4 facilitate CICR by activating both protein kinase A Epac2. Here we provide the first report that novel phosphoinositide-specific phospholipase C- (PLC-) is expressed islets Langerhans, knockout (KO) PLC- gene expression mice disrupts action to these mice. Thus, present study, which wild-type (WT) C57BL/6 mouse were loaded with photolabile...
Regulated membrane trafficking of AMPA-type glutamate receptors (AMPARs) is a key mechanism underlying synaptic plasticity, yet the pathways used by AMPARs are not well understood. In this paper, we show that AMPAR subunit GLR-1 in Caenorhabditis elegans utilizes retrograde transport pathway to regulate abundance. Mutants for rab-6.2, retromer genes vps-35 and snx-1, rme-8 failed recycle receptors, resulting turnover behavioral defects indicative diminished function. contrast, expression...
Hepatocellular carcinoma is third leading cause of cancer-related death globally. Long non-coding RNA plasmacytoma variant translocation 1 has been reported to be dysregulated and plays a crucial role in various cancers. In this study, we investigated the interactions between miR-186-5p progression hepatocellular explored functional significance 1. It was determined that significantly higher, while statistically lower tissues than adjacent normal tissues. Using gain-of-function...
Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone cosecreted with insulin and amylin from the pancreatic β-cells. corresponds to Asp 69 -Leu 102 of pro-IGF-II. Increased circulating levels pro-IGF-II complexed IGF-binding protein-2 have been implicated in high mass phenotype observed patients chronic hepatitis C infection. We assessed preptin's activities bone. dose-dependently stimulated...
Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2). One of most prominent gene targets MeCP2 brain-derived neurotrophic factor (Bdnf), potent activity-dependent synaptic development, function and plasticity. Dysfunctional BDNF signaling has been demonstrated several pathophysiological mechanisms RTT disease progression. To evaluate whether dynamics trafficking affected Mecp2 deletion,...
Farnesoid X receptor α (FXRα) as a bile acid sensor plays potent roles in multiple metabolic processes, and its antagonist has recently revealed special interests the treatment of disorders, although underlying mechanisms still remain unclear. Here, we identified that small molecule N-benzyl-N-(3-(tert-butyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino) benzamide (NDB) functioned selective human FXRα (hFXRα), crystal structure hFXRα ligand binding domain (hFXRα-LBD) complex with NDB was...