A5100438047- Sphingolipid Metabolism and Signaling
- Caveolin-1 and cellular processes
- Lipid metabolism and biosynthesis
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Peroxisome Proliferator-Activated Receptors
- Lysosomal Storage Disorders Research
- Cholesterol and Lipid Metabolism
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and disorders
- Adipose Tissue and Metabolism
- Magnesium in Health and Disease
- Alzheimer's disease research and treatments
- Cancer, Lipids, and Metabolism
- Cardiac electrophysiology and arrhythmias
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Parathyroid Disorders and Treatments
- Migraine and Headache Studies
- Blood properties and coagulation
- Calpain Protease Function and Regulation
- Spinal Cord Injury Research
- Extracellular vesicles in disease
SUNY Downstate Health Sciences University
2013-2024
Affiliated Hospital of Hebei University
2024
State University of New York
2006-2023
VA NY Harbor Healthcare System
2012-2023
Wuhan University
2019-2023
Zhongnan Hospital of Wuhan University
2019-2023
Army Medical University
2021
First Affiliated Hospital of Xi'an Jiaotong University
2019
University of Siena
2015
Oregon Health & Science University
2015
Sphingolipids play a very important role in cell membrane formation, signal transduction, and plasma lipoprotein metabolism, all of which may well have an impact on the development atherosclerosis. To investigate relationship between sphingolipid metabolism atherosclerosis, we utilized myriocin to inhibit mouse serine palmitoyl-CoA transferase (SPT), key enzyme for biosynthesis. We injected 8-week-old apoE-deficient mice with (0.3 mg/kg/every other day, intraperitoneal) 60 days. On chow...
It has been shown that inhibition of de novo sphingolipid synthesis increases insulin sensitivity. For further exploration the mechanism involved, we utilized two models: heterozygous serine palmitoyltransferase (SPT) subunit 2 (Sptlc2) gene knockout mice and sphingomyelin synthase (Sms2) mice. SPT is key enzyme in biosynthesis, Sptlc2 one its subunits. Homozygous Sptlc2-deficient are embryonic lethal. However, were viable without major developmental defects demonstrated decreased ceramide...
Sphingomyelin synthase (SMS) catalyzes the conversion of ceramide to sphingomyelin and sits at crossroads sphingolipid biosynthesis. SMS has 2 isoforms: SMS1 SMS2. Although they have same activity, are different enzymes with distinguishable subcellular localizations cell expression patterns. It is conceivable that these differences could yield consequences, in terms metabolism its related atherogenesis.We created Sms1 gene knockout mice found deficiency significantly decreased plasma, liver,...
Background— NFκB has long been regarded as a proatherogenic factor, mainly because of its regulation many the proinflammatory genes linked to atherosclerosis. Metabolism sphingomyelin (SM) suggested affect activation, but mechanism is largely unknown. SMS2 regulates SM levels in cell plasma membrane and lipid rafts potential regulate activation. Methods Results— To investigate role activation we used macrophages from knockout (KO) mice siRNA-treated HEK 293 cells. We found that target gene...
Background— Emerging clinical evidence demonstrates high prevalence of QTc prolongation and complex ventricular arrhythmias in patients with anti-Ro antibody (anti-Ro Ab)–positive autoimmune diseases. We tested the hypothesis that Abs target HERG (human ether-a-go-go–related gene) K + channel, which conducts rapidly activating delayed current, I Kr , thereby causing repolarization seen as QT interval on ECG. Methods Results— Anti-Ro Ab–positive sera, purified IgG, affinity-purified...
Genetic deficiency of the plasma phospholipid transfer protein (PLTP) in mice unexpectedly causes a substantial impairment liver secretion apolipoprotein-B (apoB), major atherogenic lipoproteins. To explore mechanism, we examined three known pathways for hepatic apoB secretory control, namely endoplasmic reticulum (ER)/proteasome-associated degradation (ERAD), post-ER pre-secretory proteolysis (PERPP), and receptor-mediated degradation, also as re-uptake. First, found that ERAD cell surface...
Sphingomyelin synthase (SMS), the last enzyme in sphingomyelin (SM) biosynthetic pathway, uses ceramide and phosphatidylcholine as substrates to produce SM diacylglycerol (DAG). To evaluate role of SMS apoptosis, we generated Chinese hamster ovary cells that stably express human SMS1 or SMS2. We found SMS2 overexpression results a significant increase cellular levels (24% 20%) DAG (35% 31%), respectively, compared with controls. Cells overexpressing were more likely undergo lysis mediated by...
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I) and generates HDL. Here, we demonstrate that ABCA1 also directly the production of apoA-I free microparticles. In baby hamster kidney (BHK) cells RAW macrophages, expression led lipid in absence released large microparticles devoid apoB apoE. We provide evidence these are an integral component classical pathway when is present accounted for approximately 30% total medium....
Sphingolipid de novo biosynthesis is related to nonalcoholic fatty liver disease or hepatic steatosis. However, the mechanism still unclear. Sphingomyelin synthase (SMS), using ceramide as one of substrates produce sphingomyelin, sits at crossroads sphingolipid biosynthesis. SMS has 2 isoforms: SMS1 and SMS2. SMS2 major isoform in liver.To investigate relationship between activity-mediated changes steatosis, we used mouse models: Sms2 liver-specific transgenic knockout mice. We found that...
After de novo biosynthesis phospholipids undergo extensive remodeling by the Lands' cycle. Enzymes involved in phospholipid have been studied extensively but not those reacylation of lysophosphopholipids. One key enzyme cycle is fatty acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT), which utilizes lysophosphatidylcholine (LysoPC) and acyl-CoA to produce various phosphatidylcholine (PC) species. Four isoforms LPCAT identified. In this study we found that LPCAT3 major hepatic isoform,...
Serine palmitoyltransferase (SPT) is the rate-limiting enzyme for sphingolipid biosynthesis. SPT has two major subunits, SPTLC1 and SPTLC2. We previously found that liver Sptlc2 deficiency in early life impairs development of adherens junctions. Here, we investigated role intestine. treated Sptlc2-Flox/villin-Cre-ER
BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension both the presence and absence of medication. This is a sham-controlled trial investigating safety efficacy RDN China. METHODS: prospective, multicenter, randomized, patient- outcome-assessor-blinded, investigated radiofrequency on standardized triple antihypertensive therapy. Eligible were randomized 1:1 to undergo using multi-electrode catheter (Iberis; Shanghai Angiocare Medical Technology,...
Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant genetic disease characterized by growth retardation, psychomotor and distinctive facial features. It primarily caused mutations in CREBBP or EP300. In this study, we aimed to describe the clinical manifestations analyses of two cases with RSTS. Clinical analysis was performed on Molecular diagnoses were made via whole exome sequencing, potential pathogenic variants filtered selected. PCR followed Sanger sequencing used verify...
Background: Brugada syndrome (BrS) is a genetic cardiac arrhythmia disorder inherited in an autosomal dominant manner, characterized by ST-segment elevation the right precordial leads (V1-V3) on electrocardiograms (ECGs). This predominantly affects young individuals with structurally normal hearts and significantly increases risk of ventricular arrhythmias sudden death (SCD). The most common genotype found among BrS patients caused mutations SCN5A gene, which lead to loss function sodium...
Sphingomyelin synthase-related protein (SMSr) synthesizes the sphingomyelin analog ceramide phosphoethanolamine (CPE) in cells. Previous cell studies indicated that SMSr is involved homeostasis and crucial for function. To further examine function vivo, we generated Smsr KO mice were fertile had no obvious phenotypic alterations. Quantitative MS analyses of plasma, liver, macrophages from revealed only marginal changes CPE as well other sphingolipid levels. Because SMS2 also has synthase...
Cell membrane phosphatidylcholine (PC) composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in PC saturation are implicated metabolic disorders. Here, we identified LPCAT3 as the major isoform of LPCAT adipose tissue and created adipocyte-specific Lpcat3–knockout mice to study lipid metabolism. Transcriptome sequencing plasma adipokine profiling were used investigate how regulates insulin signaling. deficiency reduced polyunsaturated PCs adipocyte membranes,...