A5026085971- Lipid metabolism and disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipid metabolism and biosynthesis
- Cellular transport and secretion
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Liver Disease Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Lipoproteins and Cardiovascular Health
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Cholesterol and Lipid Metabolism
- Folate and B Vitamins Research
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Metabolism, Diabetes, and Cancer
- Caveolin-1 and cellular processes
- Wnt/β-catenin signaling in development and cancer
China Academy of Space Technology
2019-2023
University of Ottawa
2012-2022
Longhua Hospital Shanghai University of Traditional Chinese Medicine
2018
Shanghai University of Traditional Chinese Medicine
2014-2018
Hospital for Sick Children
2017
SickKids Foundation
2017
University of Bonn
2017
National Clinical Research Center for Digestive Diseases
2017
University of Toronto
2017
Brown Foundation
2012
A cDNA encoding human IL-17 (hIL-17) was cloned from a CD4+ T cell library. The predicted 155-amino acids sequence contains an N-terminal signal peptide and exhibits 72% amino acid identity with HVS13, open reading frame T-lymphotropic Herpesvirus saimiri, 63% murine CTLA8. High levels of hIL-17 were induced primary peripheral blood cells upon stimulation. When expressed in CV1/EBNA cells, recombinant secreted both glycosylated nonglycosylated forms. hIL-17.Fc fusion protein supernatants...
Hepatocytes obtained from rats fed a choline-deficient diet for 3 days were cultured in medium +/- choline (100 microM) or methionine (200 microM). We investigated how deficiency affected hepatic lipogenesis, apolipoprotein synthesis, and lipoprotein secretion. The mass of triacylglycerol phosphatidylcholine secreted was increased about 3-fold 2-fold, respectively, by the addition either to cells. Similarly, stimulation secretion [3H]triacylglycerol [3H]phosphatidylcholine derived [3H]oleate...
To elucidate the role of microsomal triglyceride transfer protein (MTP) in lipoprotein assembly, MTP and apolipoprotein B-53 (apoB 53; N-terminal 53% apoB) were expressed HeLa cells. The results showed that apoB-53 could be cells with or without expression MTP. In contrast, efficient secretion required Ultracentrifugal density flotation analysis was secreted predominantly as a particle high lipoprotein. An essentially identical distribution obtained after transient McArdle RH-7777 rat...
proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulates the low-density lipoprotein (LDL) receptor (LDLR) in hepatocytes and therefore plays an important role controlling circulating levels of LDL-cholesterol. To date, relationship between PCSK9 metabolism apolipoprotein B (apoB), structural protein LDL, has been controversial remains to be clarified.We assessed impact overexpression (≈400-fold above baseline) on apoB synthesis secretion 3 mouse models: wild-type C57BL/6...
We examined the relationship between size of human apolipoprotein (apo) B and formation secretion apoB-containing lipoprotein particles. Stable transformants rat hepatoma cell line McA-RH7777 harboring a variety apoB cDNA constructs were established, these produced carboxyl-terminally truncated proteins (apoB18, -B23, -B28, -B31, -B48, -B53). Immunoblotting secreted into culture medium fractionated by equilibrium density ultracentrifugation revealed that each species was from cells. The peak...
Excess lipid induced metabolic disorders are one of the major existing challenges for society. Among many different causes disorders, overproduction and compromised catabolism triacylglycerol-rich very low density lipoproteins (VLDL) have become increasingly prevalent leading to hyperlipidemia worldwide. This review provides latest understanding in aspects VLDL assembly process, including structure-function relationships within apoB, mutations APOB causing hypobetalipoproteinemia,...
Abstract Stromal cells, infiltrating immune paracrine factors and extracellular matrix have been extensively studied in cancers. However, autocrine produced by tumor cells communications between intracellular signaling pathways the development of drug resistance, cancer stem-like (CSCs) tumorigenesis not well investigated, precise mechanism tangible approaches remain elusive. Here we reveal a new which cytokines breast after chemotherapy withdrawal activate both Wnt/ β -catenin NF- κ B...
Intracellular degradation of newly synthesized apolipoprotein (apo) B can occur at every stage the secretory pathway, from protein translation, polypeptide translocation across membrane endoplasmic reticulum (ER), to vesicular transport. The prevalence apoB each varies in different hepatic cell systems examined. Proteolysis nascent be catalyzed by ubiquitin-proteasome system cytosol, and probably unidentified ER resident proteases as well. Cytosolic lumenal molecular chaperones that...
Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin (LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators key enzymes control lipid metabolism. Dysregulation LIGHT expression T cells resulted in hypertriglyceridemia hypercholesterolemia. In low-density lipoprotein receptor-deficient mice, which lack ability to levels...
The abbreviations used are: VLDL, very low density lipoprotein; LDL, HDL, high BF, bottom fraction of salt gradient (d > 1.18 g/ml); PC, phosphatidylcholine; PE, phosphatidylethanolamine; PMME,
We have analyzed plasma lipoprotein levels in young male rats fed a choline-deficient diet for 3 days. confirmed previous studies that choline deficiency promotes 6.5-fold accumulation of triacylgycerol the liver (23.9 ± 6.0 versus 3.69 0.92 μmol/g liver) and reduction triacylglycerol concentration by 60% (0.17 0.04 0.46 0.10μmol/mL plasma). Agarose gel electrophoresis showed very low density (VLDL) were reduced rats, but high lipoproteins (HDL) was not affected. Sodium dodecyl sulfate –...
Hepatic secretion of apolipoprotein-B (apoB), the major protein atherogenic lipoproteins, is regulated through posttranslational degradation. We reported a degradation pathway, post-ER pre secretory proteolysis (PERPP), that increased by reactive oxygen species (ROS) generated within hepatocytes from dietary polyunsaturated fatty acids (PUFA). now report molecular processes which PUFA-derived ROS regulate PERPP apoB. ApoB exits ER; undergoes limited oxidant-dependent aggregation; and then,...
Hepatic assembly of triacylglycerol (TAG)-rich very low density lipoproteins (VLDL) is achieved through recruitment bulk TAG (presumably in the form lipid droplets within microsomal lumen) into VLDL precursor containing apolipoprotein (apo) B-100. We determined protein/lipid components lumenal (LLD) cells expressing recombinant human apoC-III (C3wt) or a mutant (K58E, C3KE) initially identified humans that displayed hypotriglyceridemia. Although expression C3wt markedly stimulated secretion...
Phosphatidate phosphatase-1 (PAP-1) converts phosphatidate to diacylglycerol and plays a key role in the biosynthesis of phospholipids triacylglycerol (TAG). PAP-1 activity is encoded by members lipin family, including lipin-1 (1α 1β), -2, -3. We determined effect expression on assembly secretion very low density lipoproteins (VLDL) using McA-RH7777 cells. Expression lipin-1α or -1β increased synthesis [3H]glycerol-labeled lipids under either basal- oleate-supplemented conditions. In...
Apolipoprotein (apo) C-III plays a regulatory role in VLDL lipolysis and clearance. In this study, we determined potential intracellular of apoC-III hepatic assembly secretion. Stable expression recombinant McA-RH7777 cells resulted increased secretion efficiency VLDL-associated triacylglycerol (TAG) apoB-100 gene-dosage-dependent manner. The stimulatory effect on TAG was manifested only when were cultured under lipid-rich (i.e., media supplemented with exogenous oleate) but not lipid-poor...
The mechanisms underlying disparate roles of the canonical Wnt signaling pathway in maintaining self-renewal or inducing differentiation and lineage specification embryonic stem cells (ESCs) are not clear. In this study, we provide first demonstration that versus human ESCs (hESCs) response to is predominantly determined by a two-layer regulatory circuit involving β-catenin, E-cadherin, PI3K/Akt, Slug time-dependent manner. Short-term upregulation β-catenin does lead activation T-cell factor...
Triple‐negative breast cancer ( TNBC ), the most refractory subtype of to current treatments, accounts disproportionately for majority cancer‐related deaths. This is largely due plasticity and development stem cells CSC s). Recently, distinct yet interconvertible mesenchymal‐like epithelial‐like states have been revealed in s. Thus, strategies capable simultaneously inhibiting bulk populations both mesenchymal epithelial be developed. Wnt/β‐catenin Hippo/ YAP pathways are crucial...
Previously, based on distinct requirement of microsomal triglyceride transfer protein (MTP) and kinetics (TG) utilization, we concluded that assembly very low density lipoproteins (VLDL) containing B48 or B100 was achieved through different paths (Wang, Y., McLeod, R. S., Yao, Z. (1997) <i>J. Biol. Chem.</i> 272, 12272–12278). To test if the apparent dual mechanisms were accounted for by apolipoprotein B (apoB) length, studied VLDL using transfected cells expressing various apoB forms...
Previous studies with McA-RH7777 cells showed a 15–20-min temporal delay in the oleate treatment-induced assembly of very low density lipoproteins (VLDL) after apolipoprotein (apo) B100 translation, suggesting post-translational process. Here, we determined whether apoB100-VLDL occurred within endoplasmic reticulum (ER) or post-ER compartments using biochemical and microscopic techniques. At steady state, apoB100 distributed throughout ER Golgi, which were fractionated by Nycodenz gradient...