A5039639549- Endoplasmic Reticulum Stress and Disease
- Hepatitis C virus research
- SARS-CoV-2 and COVID-19 Research
- Phagocytosis and Immune Regulation
- Liver Disease Diagnosis and Treatment
- interferon and immune responses
- Viral Infections and Outbreaks Research
- Autophagy in Disease and Therapy
- Viral gastroenteritis research and epidemiology
- Protein Structure and Dynamics
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
- Hepatitis B Virus Studies
- Lipid metabolism and biosynthesis
- Systemic Lupus Erythematosus Research
- Animal Virus Infections Studies
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Diabetes Treatment and Management
- Bacteriophages and microbial interactions
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Adipose Tissue and Metabolism
- HER2/EGFR in Cancer Research
- Breast Cancer Treatment Studies
Montreal Clinical Research Institute
2020-2023
Université de Montréal
2020-2023
New York University
2008-2020
Rockefeller University
2015-2020
Institut Pasteur
2006-2009
Cellular imbalances of cholesterol and fatty acid metabolism result in pathological processes, including atherosclerosis metabolic syndrome. Recent work from our group others has shown that the intronic microRNAs hsa-miR-33a hsa-miR-33b are located within sterol regulatory element-binding protein-2 -1 genes, respectively, regulate homeostasis concert with their host genes. Here, we show miR-33a -b also genes involved insulin signaling. target key enzymes regulation oxidation, carnitine O...
SARS-CoV-2, the etiological agent of COVID-19, has so far resulted in >6.1 million deaths worldwide. The spike protein (S) virus directs infection lungs and other tissues by binding angiotensin-converting enzyme 2 (ACE2) receptor.
Abstract Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a differentiation protocol that uses transwell filters generate columnar polarized with clearly defined basolateral and apical membranes separated by tight junctions. We show secrete cargo directionally: Albumin, urea, lipoproteins are secreted basolaterally,...
The possible role of candidate receptors in the cellular penetration HCV from serum infected patients remains unclear. SR-BI/Cla1 interacts with plasma HDL, native and modified LDL, VLDL, facilitates cholesterol efflux to lipoprotein acceptors. binds E2 protein pseudotypes via HVR1 envelope glycoprotein. Our data reveal that functional expressed on surface CHO cells mediates binding uptake sera patients. Interaction between is not sensitive either anti-E2 or anti-HVR1 antibodies but...
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,...
Apolipoprotein-B100 (apoB100) is the essential protein for assembly and secretion of very low density lipoproteins (VLDL) from liver. The hepatoma HepG2 cell line has been choice study synthesis human apoB-100. Despite general use cells to apoB100 metabolism, they secrete relatively dense, lipid-poor particles compared with VLDL secreted in vivo. Recently, Huh-7 were adopted as an alternative model cells, implicit assumption that superior some respects lipoprotein including secretion. In...
The host-virus interactions leading to cell infection with hepatitis C virus (HCV) are not fully understood. tetraspanin CD-81 and human scavenger receptor SR-BI/Cla1 major receptors mediating entry. However, HCV in patients' sera is associated lipoproteins infectious potential of the depends on particles. We show here that lipoprotein lipase (LPL), targeting triglyceride-rich (TRL) liver, mediates binding internalization different types cells, acting as a bridge between virus-associated...
Early events leading to the establishment of hepatitis C virus (HCV) infection are not completely understood. We show that intact and dynamic microtubules play a key role in initiation productive HCV infection. Microtubules were required for entry into cells, as evidenced using pseudotypes presenting envelope proteins on their surface. Studies carried out recent infectious model revealed also an essential early, postfusion steps cycle. Moreover, low concentrations vinblastin nocodazol,...
Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for infectivity SARS-CoV-2, which requires cleavage its spike protein (S) at two sites: S1/S2 S2′. This study investigates implication cholesterol-regulating SKI-1 PCSK9 SARS-CoV-2 entry. The assays used were cell-to-cell fusion HeLa cells pseudoparticle into Calu-3 cells. increased by enhancing activation SREBP-2, whereas...
Secretory cells produce diverse cargoes, yet how they regulate concomitant secretory traffic remains insufficiently explored. Rab GTPases control intracellular vesicular transport. To map secretion pathways, we generated a library of lentivirus-expressed dominant-negative mutants and used it in large-scale screen to identify regulators hepatic lipoprotein secretion. We identified several candidate including those mediated by Rab11 Rab8. Surprisingly, inhibition Rab1b, the major regulator...
ABSTRACT DNAJC14, a heat shock protein 40 (Hsp40) cochaperone, assists with Hsp70-mediated folding. Overexpressed DNAJC14 is targeted to sites of yellow fever virus (YFV) replication complex (RC) formation, where it interacts viral nonstructural (NS) proteins and inhibits RNA replication. How RCs are assembled the roles chaperones in this coordinated process largely unknown. We hypothesized that diverted from their normal cellular quality control function play similar during infection. Here,...
Both in humans and animal models, an acute increase plasma insulin levels, typically following meals, leads to transient depression of hepatic secretion very low density lipoproteins (VLDL). One contributing mechanism for the decrease VLDL is enhanced degradation apolipoprotein B100 (apoB100), which required formation. Unlike nascent apoB100, occurs endoplasmic reticulum (ER), insulin-stimulated apoB100 post-ER inhibited by pan-phosphatidylinositol (PI)3-kinase inhibitors. It unclear,...
VLDL is produced by the liver. Its major protein apoB100. Docosahexaenoic acid (DHA), a dietary polyunsaturated fatty (PUFA), reduces levels and used therapeutically for hypertriglyceridemia. In model systems, DHA lowers secretion inducing presecretory apoB100 degradation, process dependent on PUFA-derived lipid peroxides. We hypothesized that superoxide (SO) was participant in DHA-induced given its promotion of peroxidation. SO metabolism, rat hepatoma McArdle cells, were either decreased...
Inhibition of the binding enveloped viruses surface glycoproteins to host cell receptor(s) is a major target vaccines and constitutes an efficient strategy block viral entry infection various cells tissues. Cellular usually requires fusion envelope with plasma membranes. Such mechanism often preceded by “priming” and/or “activation” steps requiring limited proteolysis glycoprotein expose fusiogenic domain for membrane juxtapositions. The 9-membered...
One mechanism of the lipid-lowering effects fish oil n-3 fatty acids [e.g., docosahexaenoic acid (DHA)] in cell and animal models is induced hepatic apolipoprotein B100 (apoB) presecretory degradation. This degradation occurs post-endoplasmic reticulum, but whether DHA induces it before or after intracellular VLDL formation remains unanswered. We found McA-RH7777 rat cells that oleic (OA) treatments allowed pre-VLDL particles their transport to Golgi, but, contrast OA, with failed...
Apolipoprotein E ( ApoE ), a component of very‐low‐density and high‐density lipoproteins, participates in many aspects lipid transport the bloodstream. Underscoring its important functions, isoforms have been associated with metabolic circulatory disease. is also incorporated into hepatitis C virus HCV ) particles, promotes their production infectivity. Live cell imaging analysis behavior during secretion from producing cells thus has potential to reveal details regarding lipoprotein...
ABSTRACT The spîke (S)-protein of SARS-CoV-2 binds ACE2 and requires proteolytic “priming” at P R RA 685 ↓ into S1 S2 (cleavage S1/S2), “fusion-activation” a S2’ site for viral entry. In vitro , Furin cleaved peptides mimicking the S1/S2 cleavage more efficiently than putative S2’, whereas TMPRSS2 inefficiently both sites. HeLa cells Furin-like enzymes mainly during intracellular protein trafficking, processing by KPS KR 815 was strongly enhanced ACE2, but not optimized K RR mutant (μS2’),...
Background & AimsHepatitis C virus (HCV) is a leading cause of chronic liver diseases and the most common indication for transplantation in United States. HCV particles blood infected patients are characterized by heterogeneous buoyant densities, likely owing to association with lipoproteins. However, clinical isolates not infectious vitro relative infectivity respect their density therefore cannot be determined, pointing need better vivo model systems.MethodsTo analyze evolution...
Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for infectivity SARS-CoV-2. This study investigated implication two cholesterol-regulating SKI-1 PCSK9 SARS-CoV-2 entry. used cell-to-cell fusion assays HeLa cells pseudoparticle into Calu-3 cells. increases by enhancing activation SREBP-2, whereas reduces promoting degradation ACE2. Metalloprotease sensitive to enhanced...
Disclaimer Statement The author has withdrawn this manuscript due to a duplicate posting of number 423106. Therefore, the does not wish work be cited as reference for project. If you have any questions, please contact corresponding (Nabil G. Seidah at seidahn@ircm.qc.ca .