A5038797261- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Liver Disease Diagnosis and Treatment
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Lipid metabolism and biosynthesis
- Mitochondrial Function and Pathology
- Fungal and yeast genetics research
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Bioinformatics and Genomic Networks
- Eicosanoids and Hypertension Pharmacology
- Lysosomal Storage Disorders Research
- Adipose Tissue and Metabolism
- Erythrocyte Function and Pathophysiology
- Pancreatic function and diabetes
- Sleep and Wakefulness Research
- Gene expression and cancer classification
- Plant Reproductive Biology
- Liver Disease and Transplantation
- Diet, Metabolism, and Disease
- ATP Synthase and ATPases Research
Hunter Holmes McGuire VA Medical Center
2018-2025
Virginia Commonwealth University
2018-2025
Veterans Health Administration
2024
Washington University in St. Louis
2022
Children's Hospital of Richmond at VCU
2020-2022
VCU Massey Comprehensive Cancer Center
2021
Virginia Cancer Institute
2021
University of Arizona
2020
Medical University of South Carolina
2009-2018
Ralph H. Johnson VA Medical Center
2007-2017
Accumulating data support a role for bioactive lipids as mediators of lipotixicity in cardiomyocytes. One class these, the ceramides, constitutes family molecules that differ structure and are synthesized by distinct enzymes, ceramide synthase (CerS)1-CerS6. Data specific ceramides enzymes catalyze their formation play roles cell function. In mouse model diabetic cardiomyopathy, sphingolipid profiling revealed increases not only CerS5-derived but also very long chain (VLC) derived from...
Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence traditional risk factors, is a major contributor to increased heart type 2 diabetes patients. In rodent models DbCM, dysfunction have been shown depend upon saturated fatty acid (SFA) oversupply de novo sphingolipid synthesis. However, it not known whether these effects are mediated by bulk SFAs sphingolipids or individual lipid species. this report, we demonstrate that diet high SFA induced...
Cytochromes P450 of the CYP2Cand CYP4A gene subfamilies metabolize arachidonic acid to 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) 19- 20-hydroxyeicosatetraenoic (HETEs), respectively. Abundant functional studies indicate that EETs HETEs display powerful often opposing biological activities as mediators ion channel activity regulators vascular tone systemic blood pressures. Incubation 14,15-EETs with microsomal purified forms rat isoforms led rapid NADPH-dependent...
Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity the regulation of autophagy cell type specific. Despite adverse consequences on cardiac structure function, contribution altered response to fatty acid overload incompletely understood. Here, we report suppression autophagosome clearance activation NADPH oxidase (Nox)2 both high fat-fed murine hearts palmitate-treated H9C2 cardiomyocytes (CMs). Defective secondary...
Abstract The importance of MCL-1 in leukemogenesis has prompted development antagonists e.g., S63845, MIK665. However, their effectiveness acute myeloid leukemia (AML) is limited by compensatory accumulation via the ubiquitin proteasome system. Here, we investigated mechanisms which kinase inhibitors with Src inhibitory activity bosutinib (SKI-606) might circumvent this phenomenon. antagonist/SKI-606 co-administration synergistically induced apoptosis diverse AML cell lines. Consistently, or...
Periodontal disease is more prevalent and severe in patients with diabetes than nondiabetic patients. In addition to diabetes, a large number of studies have demonstrated an association between obesity chronic periodontal disease. However, the underlying mechanisms not been well understood. Since plasma free fatty acids (FAs) are elevated obese saturated FAs such as palmitic acid (PA) shown increase host inflammatory response, we sought find out how PA interacts lipopolysaccharide (LPS),...
Much data implicate saturated fatty acids in deleterious processes associated with obesity, diabetes, and the metabolic syndrome. Many of these changes may be due to aberrant generation bioactive lipids when acid availability tissues is increased. On other hand, studies are emerging that monounsaturated oleate protection from fat mediated toxicity; however, mechanisms not well understood. Our demonstrate a novel role for palmitate increasing mRNA encoding DES1, which enzyme responsible...
Steatohepatitis occurs in up to 20% of patients with fatty liver disease and leads its primary outcomes, including fibrosis, cirrhosis, increased risk hepatocellular carcinoma. Mechanisms that mediate this inflammation are major interest. We previously showed overload saturated acids, such as which metabolic syndrome, induced sphingosine kinase 1 (SphK1), an enzyme generates sphingosine-1-phosphate (S1P). While data suggest beneficial roles for S1P some contexts, we hypothesized it may...
Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM mice humans, patients anthracycline-induced failure, heterozygosity increases Dox-induced mortality. In the setting of Dox stress, our studies suggest can help sustain myocardial autophagic flux a post-transcriptional manner, attenuate cardiotoxicity, prevent lysosomal injury.
Studies in skeletal muscle demonstrate that elevation of plasma FFAs increases the sphingolipid ceramide. We aimed to determine impact FFA oversupply on total profiles a model. C2C12 myotubes were treated with palmitate (PAL). Lipidomics analysis revealed pleiotropic effects PAL cell sphingolipids not limited ceramides. (13)C labeling demonstrated activated several branches synthesis by distinct mechanisms. Intriguingly, increased sphingosine-1-phosphate independently de novo synthesis....
The Izh2p protein from <i>Saccharomyces cerevisiae</i> belongs to the newly characterized progestin and adipoQ receptor (PAQR) superfamily of receptors whose mechanism signal transduction is still unknown. functions as a for plant PR-5 defensin osmotin has pleiotropic effects on cellular biochemistry. One example this pleiotropy Izh2p-dependent repression <i>FET3</i>, gene involved in iron-uptake. Although physiological purpose <i>FET3</i> by matter speculation, it provides reporter with...
Sphingolipids and phosphoinositides both play signaling roles in Saccharomyces cerevisiae. Although previous data indicate independent functions for these two classes of lipids, recent genetic studies have suggested interactions between phosphatidylinositol (PtdIns) phosphate effectors sphingolipid biosynthetic enzymes. The present study was undertaken to further define the effects 4-phosphate (PtdIns(4)P) metabolism on cell metabolism. presented that deletion SAC1, a gene encoding...
Nonalcoholic fatty liver disease (NAFLD), a leading cause of dysfunction, is metabolic that begins with steatosis. Sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate (S1P), have recently received attention for their potential roles in insulin resistance hepatic FTY720/fingolimod, prodrug the treatment multiple sclerosis, phosphorylated vivo to its active form by sphingosine kinase 2 has been shown interfere actions S1P inhibit biosynthesis. Therefore, this study we...
Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, cellular roles are not completely understood. Sphingolipids produced by serine palmitoyltransferase enzyme, canonically composed 2 subunits, SPTLC1 (serine long chain base subunit 1) SPTLC2 2). Noncanonical sphingolipids a more recently described subunit, SPTLC3 3).
Recent studies are beginning to implicate sphingolipids in the heat stress response. In yeastSaccharomyces cerevisiae, has been shown activate de novo biosynthesis of sphingolipids, whereas mammalian cells sphingolipid ceramide implicated shock responses. current study, we found an increase mass Molt-4 response shock, corroborating findings HL-60 cells. Increased was determined be fromde by two major lines evidence. First, accumulation dependent upon activities both synthase and serine...
The heat stress response of Saccharomyces cerevisiae is characterized by transient cell cycle arrest, altered gene expression, degradation nutrient permeases, trehalose accumulation, and translation initiation shock proteins. Importantly also induces de novo sphingolipid synthesis upon which many these subprograms the depend. Despite extensive data addressing roles for sphingolipids in stress, mechanism(s) remains unknown. This study was undertaken to determine events and/or factors required...