A5011102538- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Drug Transport and Resistance Mechanisms
- Nitric Oxide and Endothelin Effects
- Immune cells in cancer
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- PI3K/AKT/mTOR signaling in cancer
- Amino Acid Enzymes and Metabolism
- Fibroblast Growth Factor Research
- Mast cells and histamine
- Inflammasome and immune disorders
- Caveolin-1 and cellular processes
- Kruppel-like factors research
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- Platelet Disorders and Treatments
- Mitochondrial Function and Pathology
- Lysosomal Storage Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Enzyme function and inhibition
National Institute of Mental Health
2002-2023
Virginia Commonwealth University
2013-2023
VCU Massey Comprehensive Cancer Center
2013-2022
Virginia Cancer Institute
2010-2022
Niigata University
2014-2018
University at Buffalo, State University of New York
2018
Roswell Park Comprehensive Cancer Center
2018
Yokohama City University Medical Center
2013-2018
Yokohama City University
2013-2018
Chigasaki Rehabilitation College
2018
Epigenetic Signals The lipid sphingosine-1-phosphate (S1P) is a signaling molecule that binds to receptors on the cell surface initiate biochemical changes control range of biological processes from growth and survival immune reactions. Hait et al. (p. 1254 ) report S1P can also function by direct binding nuclear enzymes, histone deacetylases (HDACs) 1 2. enzyme generates S1P, sphingosine kinase 2 (ShpK2) present in nucleus complexes with HDAC1 HDAC2. Generation its HDACs inhibited...
Sphingosine-1-phosphate (SPP) has diverse biological functions acting inside cells as a second messenger to regulate proliferation and survival, extracellularly, ligand for G protein-coupled receptors of the endothelial differentiation gene-1 subfamily. Based on sequence homology murine human sphingosine kinase-1 (SPHK1), which we recently cloned (Kohama, T., Oliver, A., Edsall, L., Nagiec, M. M., Dickson, R., Spiegel, S. (1998) <i>J. Biol. Chem.</i> 273, 23722–23728), have now type mouse...
The potent sphingolipid metabolite sphingosine 1-phosphate is produced by phosphorylation of catalyzed kinase (SphK) types 1 and 2. In contrast to pro-survival SphK1, the putative BH3-only protein SphK2 inhibits cell growth enhances apoptosis. Here we show that catalytic activity also contributes its ability induce Overexpressed increased cytosolic free calcium induced serum starvation. Transfer mitochondria was required for SphK2-induced apoptosis, as death cytochrome c release abrogated...
EDG-1 is a heterotrimeric guanine nucleotide binding protein–coupled receptor (GPCR) for sphingosine-1-phosphate (SPP). Cell migration toward platelet-derived growth factor (PDGF), which stimulates sphingosine kinase and increases intracellular SPP, was dependent on expression of EDG-1. Deletion edg-1 or inhibition suppressed chemotaxis PDGF also activation the small guanosine triphosphatase Rac, essential protrusion lamellipodia forward movement. Moreover, activated EDG-1, as measured by...
Mast cells play a pivotal role in inflammatory and immediate-type allergic reactions by secreting variety of potent mediators, including sphingosine-1-phosphate (S1P). However, it is not known how S1P released from cells. Here, we report that exported mast independently their degranulation demonstrate mediated ATP binding cassette (ABC) transporters. Constitutive antigen-stimulated release was inhibited MK571, an inhibitor ABCC1 (MRP1), but inhibitors ABCB1 (MDR-1, P-glycoprotein). Moreover,...
We have examined cytokine regulation of nitric oxide synthase (NOS) in human umbilical vein endothelial cells (HUVEC). 24-h treatment with IFN-gamma (200 U/ml) plus TNF or IL-1 beta (5 increased NOS activity HUVEC lysates, measured as conversion [14C]L-arginine to [14C]L-citrulline. Essentially, all these was calcium dependent and membrane associated. Histamine-induced release, by chemiluminescence, greater cytokine-treated than control cells. Paradoxically, steady-state mRNA levels fell 94...
The potent lipid mediator sphingosine-1-phosphate (S1P) regulates diverse physiological processes by binding to 5 specific GPCRs, although it also has intracellular targets. Here, we demonstrate that S1P, produced in the mitochondria mainly sphingosine kinase 2 (SphK2), binds with high affinity and specificity prohibitin (PHB2), a highly conserved protein mitochondrial assembly function. In contrast, S1P did not bind closely related PHB1, which forms large, multimeric complexes PHB2. from...
Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates myriad important cellular processes, including growth, survival, cytoskeleton rearrangements, motility, and immunity. Here we report treatment of Jurkat U937 leukemia cells with the pan-sphingosine kinase (SphK) inhibitor N,N-dimethylsphingosine to block S1P formation surprisingly caused large increase in expression SphK1 concomitant induction apoptosis. Another SphK inhibitor, D,L-threo-dihydrosphingosine, also induced...
The onset of neurologic symptoms in a child who had markedly elevated blood phenylalanine levels during the first two weeks life and was promptly treated with low diet, excellent control serum levels, suggested that this an unusual form phenylketonuria. In assays components hydroxylating system (open liver biopsy at 14 months), activity hydroxylase 20 per cent average normal adult value. By contrast, no dihydropteridine reductase detected patient's liver, brain or cultured skin fibroblasts....
Abstract Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that promotes breast cancer progression by diverse mechanisms remain somewhat unclear. Here we report pharmacologic evidence of critical role for sphingosine kinase 1 (SphK1) in producing S1P and mediating tumor-induced hemangiogenesis lymphangiogenesis murine model metastasis. levels increased both the tumor circulation. In agreement, serum were significantly elevated stage IIIA human patients, compared with...
Sphingosine 1-phosphate (S1P), a potent sphingolipid mediator produced by sphingosine kinase isoenzymes (SphK1 and SphK2), regulates diverse cellular processes important for breast cancer progression acting in an autocrine and/or paracrine manner. Here we show that SphK1, but not SphK2, increased S1P export from MCF-7 cells. Whereas both estradiol (E2) epidermal growth factor-activated SphK1 production of S1P, only E2 stimulated rapid release dihydro-S1P E2-induced required estrogen...