A5090983361- Cellular transport and secretion
- Cholesterol and Lipid Metabolism
- Lipid Membrane Structure and Behavior
- Lipid metabolism and biosynthesis
- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Protein Kinase Regulation and GTPase Signaling
- Nuclear Structure and Function
- Peroxisome Proliferator-Activated Receptors
- Caveolin-1 and cellular processes
- Diet, Metabolism, and Disease
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Metabolism and Genetic Disorders
- Retinoids in leukemia and cellular processes
- Calcium signaling and nucleotide metabolism
- Liver Disease Diagnosis and Treatment
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Lysosomal Storage Disorders Research
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Protein Degradation and Inhibitors
- Neuroscience and Neuropharmacology Research
- RNA Interference and Gene Delivery
Dalhousie University
2015-2024
University of Geneva
2020
Atlantic School of Theology
2018
Pediatrics and Genetics
2008
Izaak Walton Killam Health Centre
2001
University of Alberta
1987-1993
The University of Texas Southwestern Medical Center
1989-1992
Howard Hughes Medical Institute
1989
University of British Columbia
1986
A cDNA encoding a cytoplasmic oxysterol binding protein was expressed at high levels by transfection in animal cells. This binds oxysterols such as 25-hydroxycholesterol that regulate sterol metabolism transcriptional and posttranscriptional effects. In the transfected cells, some of (OSBP) distributed diffusely cytoplasm, bound to small vesicles near nucleus, revealed indirect immunofluorescence. Upon addition 25-hydroxycholesterol, most OSBP became concentrated large perinuclear structures...
Sphingomyelin (SM) and cholesterol are coregulated metabolically associate physically in membrane microdomains involved cargo sorting signaling. One mechanism for regulation of this metabolic interface involves oxysterol binding protein (OSBP) via high-affinity to regulators homeostasis activation SM synthesis at the Golgi apparatus. Here, we show that OSBP endoplasmic reticulum (ER)-to-Golgi ceramide transport (CERT). RNA interference (RNAi) experiments Chinese hamster ovary (CHO)-K1 cells...
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large gene family that differentially localize to organellar membranes, reflecting functional role in sterol signaling and/or transport. OSBP partitions between the endoplasmic reticulum (ER) Golgi apparatus where it imparts sterol-dependent regulation of ceramide transport sphingomyelin synthesis. ORP9L also is localized ER–Golgi, but its secretion lipid unknown. Here we demonstrate partitioning...
Lipoprotein cholesterol is delivered to the limiting membrane of late endosomes/lysosomes (LELs) by Niemann-Pick C1 (NPC1). However, mechanism transport from LELs endoplasmic reticulum (ER) poorly characterized. We report that oxysterol-binding protein-related protein 1L (ORP1L) necessary for this stage export. CRISPR-mediated knockout ORP1L in HeLa and HEK293 cells reduced esterification level NPC1 cells, it increased expression sterol-regulated genes de novo synthesis, indicative a block...
Feedback repression of the genes encoding low density lipoprotein receptor and several enzymes cholesterol biosynthetic pathway is mediated by 25-hydroxycholestero1 other oxysterols.In this study, we have cloned a rabbit cDNA an oxysterol-binding protein that may play role in regulation.The predicted amino acid sequence revealed 809 acids with two distinctive features: 1) glycine-and alanine-rich region (63% 80 residues) at NH2 terminus, 2) 35residue leucine zipper motif mediate previously...
Abstract Phosphatidylethanolamine (PE) N-methyltransferase catalyzes the synthesis of phosphatidylcholine by stepwise transfer methyl groups from S-adenosylmethionine to amino head group PE. PE was solubilized a microsomal membrane fraction rat liver using nonionic detergent Triton X-100 and purified apparent homogeneity. Specific activities with PE, phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-N,N-dimethylethanolamine (PDME) as substrates were 0.63, 8.59, 3.75 mumol/min/mg...
Protein kinase D (PKD) plays a critical role at the trans-Golgi network by regulating fission of transport carriers destined for plasma membrane. Two known Golgi-localized PKD substrates, PI4-kinase IIIbeta and ceramide transfer protein CERT, mediate signaling to influence vesicle trafficking membrane sphingomyelin synthesis, respectively. is recruited activated Golgi through interaction with diacylglycerol, pool which generated as by-product synthesis from ceramide. Here we identify novel...
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) comprise a large gene family with sterol/lipid transport regulatory activities. ORP4 (OSBP2) is closely related paralogue of OSBP, but its function unknown. Here we show that binds similar sterol lipid ligands as OSBP other ORPs uniquely required for the proliferation survival cultured cells. Recombinant ORP4L variant without pleckstrin homology (PH) domain (ORP4S) bind 25-hydroxycholesterol extract transfer cholesterol...
Curcumin, the principal curcuminoid of tumeric, has potent anticancer activity. To determine mechanism curcumin-induced cytotoxicity in prostate cancer cells, we exposed PC3 carcinoma cells to 25 100 μ M curcumin for 24 72 h. Curcumin treatment caused time- and dose-dependent induction apoptosis depletion cellular reduced glutathione (GSH). Exogenous GSH its precursor N-acetyl-cysteine, but not ascorbic acid (AA) or ebselen, decreased accumulation also prevented DNA fragmentation. The...
The cytidine diphosphate-choline (Kennedy) pathway culminates with the synthesis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by choline/ethanolamine phosphotransferase 1 (CEPT1) in endoplasmic reticulum (ER), PC choline (CHPT1) Golgi apparatus. Whether PE synthesized CEPT1 CHPT1 ER apparatus has different cellular functions not been formally addressed. Here, we used CRISPR editing to generate CEPT1-and CHPT1-KO U2OS cells assess differential contribution enzymes feedback...
Oxysterol-binding protein (OSBP) is a high-affinity receptor for variety of oxysterols, such as 25-hydroxycholesterol, that down-regulate cholesterol synthesis and stimulate esterification. To examine potential role OSBP in regulating metabolism, we stably overexpressed this Chinese-hamster ovary (CHO)-K1 cells. Compared with mock-transfected controls, several cell lines overexpressing wild-type (CHO-OSBP) displayed 50% decrease cholesteryl ester when cultured medium delipidated serum,...
Oxysterol-binding protein (OSBP) is the prototypical member of a class phospholipid and oxysterol-binding proteins that interacts with Golgi apparatus regulates lipid cholesterol metabolism. As result recent sequencing efforts, eleven other OSBP-related (ORPs) have been identified in humans. We investigated structure, activity, cellular localization function ORP4 (also designated OSBP2 or HLM), homologue shares highest degree similarity OSBP. Two cDNAs were identified: full-length containing...
Cholesterol and sphingomyelin (SM) associate in raft domains are metabolically coregulated. One aspect of coordinate regulation occurs the Golgi apparatus where oxysterol binding protein (OSBP) mediates sterol-dependent activation ceramide transport (CERT) activity SM synthesis. Because CERT transfer is dependent on its phosphatidylinositol 4 phosphate [PtdIns(4)P]-specific pleckstrin homology domain, we investigated whether OSBP involved a Golgi-associated PtdIns 4-kinase (PI4K). Cell...