A5056557589- Sphingolipid Metabolism and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Endoplasmic Reticulum Stress and Disease
- Liver Disease Diagnosis and Treatment
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Cellular transport and secretion
- Diet, Metabolism, and Disease
- Peptidase Inhibition and Analysis
- Metabolism, Diabetes, and Cancer
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- PI3K/AKT/mTOR signaling in cancer
- Angiogenesis and VEGF in Cancer
- Estrogen and related hormone effects
- Peroxisome Proliferator-Activated Receptors
- Receptor Mechanisms and Signaling
- Cell death mechanisms and regulation
- Diabetes Treatment and Management
- Retinoids in leukemia and cellular processes
- Berberine and alkaloids research
- Lipid metabolism and disorders
- Erythrocyte Function and Pathophysiology
- Signaling Pathways in Disease
Fudan University
2014-2024
Zhongshan Hospital
2014-2024
University of Saskatchewan
2023-2024
OncoRay
2022
TU Dresden
2022
Helmholtz-Zentrum Dresden-Rossendorf
2022
University Hospital Carl Gustav Carus
2022
Jinzhou Medical University
2017-2022
Huashan Hospital
2018-2020
The First Affiliated Hospital, Sun Yat-sen University
2015-2020
Vascular endothelial growth factor (VEGF) is a potent cell mitogen which mediates its effects by binding to tyrosine kinase receptors. We have characterized the VEGF-activated intracellular signal transduction pathway in bovine aortic cells and correlated this mitogenic effects. VEGF induced concentration- time-dependent increases protein C (PKC) activation with maximum of 2.2-fold above basal level at 5 x 10(-10) M within 10 min as measured both situ translocation assays. Immunoblotting...
Similar vascular pathological conditions are observed in diabetic animals and those with diet-induced hypergalactosemia. Both diabetes hypergalactosemia believed to cause dysfunction via a common biochemical mechanism. In this study, we have found that both the short term (2–4 months) can increase total diacylglycerol (DAG) levels by 52 ± 9 74 13% retina aorta, respectively, of dogs, 94 78 11% dogs as compared normal control (P < 0.01). The elevation DAG was maintained for 5 years...
The signaling pathways that couple tumor necrosis factor-α (TNFα) receptors to functional, especially inflammatory, responses have remained elusive. We report here TNFα induces endothelial cell activation, as measured by the expression of adhesion protein E-selectin and vascular molecule-1, through sphingosine kinase (SKase) pathway. Treatment human umbilical vein cells with resulted in a rapid SKase activation 1-phosphate (S1P) generation. S1P, but not ceramide or sphingosine, was potent...
Tumor necrosis factor-α (TNF) receptor-associated factor 2 (TRAF2) is one of the major mediators TNF receptor superfamily transducing signaling to various functional targets, including activation NF-κB, JNK, and antiapoptosis. We investigated how TRAF2 mediates differentially distinct downstream signals. now report a novel mechanism TRAF2-mediated signal transduction revealed by an association with sphingosine kinase (SphK), lipid that responsible for production 1-phosphate. identified...
Sphingosine kinase (SK) 1 catalyzes the formation of bioactive lipid sphingosine 1-phosphate, and has been implicated in several biological processes mammalian cells, including enhanced proliferation, inhibition apoptosis, oncogenesis. Human SK (hSK) possesses high instrinsic catalytic activity which can be further increased by a diverse array cellular agonists. We have shown previously that this activation occurs as direct consequence extracellular signal-regulated 1/2-mediated...
The ability of high density lipoproteins (HDL) to inhibit cytokine-induced adhesion molecule expression has been demonstrated in their protective function against the development atherosclerosis and associated coronary heart disease. A key event atherogenesis is endothelial activation induced by a variety stimuli such as tumor necrosis factor-α (TNF), resulting various proteins. We have recently reported that sphingosine 1-phosphate, generated kinase activation, mediating TNF-induced protein...
The transactivation of enhanced growth factor receptor (EGFR) by G protein–coupled (GPCR) ligands is recognized as an important signaling mechanism in the regulation complex biological processes, such cancer development. Estrogen (E2), which a steroid hormone that intimately implicated breast cancer, has also been suggested to function via EGFR transactivation. In this study, we demonstrate E2-induced human cells driven novel system controlled lipid kinase sphingosine kinase-1 (SphK1). We...
We have reported that membranous protein kinase C (PKC) activities and total diacylglycerol (DAG) levels are increased in the heart aorta of diabetic rats, which cannot be easily reversed by euglycemic control. However, insulin treatment, achieved euglycemia, can prevent increase PKC DAG levels. Chronic exposure to elevated glucose (5.5 vs. 22 mM) cultured bovine rat aortic endothelial cells smooth muscle 31, 140, 143%, respectively, only after 3 days incubation. Glyceraldehyde, stimulate de...
Nonalcoholic fatty liver disease (NAFLD) is a common disorder that currently lacks effective treatment. Berberine (BBR), botanic compound isolated from traditional Chinese medicine, exhibits potent therapeutic potential for the metabolic disease. The current study aimed to understand mechanisms underlying effect of BBR in NAFLD. We performed systematical analyses on hepatic expression profiles mRNAs and long noncoding RNAs (lncRNAs) high-fat diet (HFD)-induced steatotic animal model with or...
Sphingosine kinase (SK) catalyzes the formation of sphingosine 1-phosphate (S1P), a lipid messenger that plays an important role in variety mammalian cell processes, including inhibition apoptosis and stimulation proliferation. Basal levels S1P cells are generally low but can increase rapidly when exposed to various agonists through rapid transient activation SK activity. To date, elucidation exact signaling pathways affected by these elevated has relied on use inhibitors known have direct...
Inhibition of Na+,K(+)-ATPase activity by hyperglycemia could be an important etiological factor chronic complications in diabetic patients. The biochemical mechanism underlying hyperglycemia's inhibitory effects has been thought to involve the alteration protein kinase C (PKC) pathway since agonists PKC can normalize hyperglycemia-induced inhibition activity. Paradoxically, elevated glucose levels and diabetes have shown increase activities vascular cells. present study tested hypothesis...
Sphingosine 1-phosphate (S1P) is a novel lipid messenger that has important roles in wide variety of mammalian cellular processes including growth, differentiation and death. Basal levels S1P cells are generally low, but can increase rapidly transiently when exposed to mitogenic agents other stimuli. This largely due increased activity sphingosine kinase (SK), the enzyme catalyses its formation. In current study we have purified, cloned characterized first human SK obtain better...
C-reactive protein (CRP), a well-recognized marker of atherosclerosis, has recently been suggested to have direct proinflammatory effect. The constitutive expression low levels CRP in normal plasma suggests the likelihood that natural factor exists neutralize effect CRP. This factor(s) not yet identified. Method and Results- was measured by induction inflammatory adhesion molecules human umbilical vein endothelial cells (HUVECs). We show significantly induced upregulation both mRNA levels....
Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report treatment with 17beta-estradiol (E2) activates a novel pathway via activation sphingosine kinase (SphK) MCF-7 cells. We found E2 has dual actions to stimulate SphK activity, i.e. rapid and transient mediated by putative membrane G protein-coupled receptors (ER) delayed but prolonged relying on the transcriptional activity ER. The E2-induced consequently...
FTY720, a sphingosine analog, is novel immunosuppressant currently undergoing multiple clinical trials for the prevention of organ transplant rejection and treatment various autoimmune diseases. Recent studies indicate an additional cytotoxic effect FTY720 its preclinical efficacy in variety cancer models, yet underlying mechanisms remain unclear. We demonstrate here first time that exhibits potent, dose- time-dependent human ovarian cells, even cells are resistant to cisplatin, commonly...
Berberine (BBR) shows promising effects in the treatment of nonalcoholic fatty liver disease (NAFLD) by influencing various metabolic aspects. Inhibition mitochondrial β-oxidation (β-OX) participates pathogenesis NAFLD. Silent mating-type information regulation 2 homolog 3 (SIRT3) has been reported to regulate β-OX deacetylating its substrate, long-chain acyl-coenzyme A dehydrogenase (LCAD). This study aimed explore whether BBR can promote and role SIRT3 as well mechanisms underlying on...