A5072315648- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Erythrocyte Function and Pathophysiology
- Caveolin-1 and cellular processes
- Protein Kinase Regulation and GTPase Signaling
- Lysosomal Storage Disorders Research
- Inflammasome and immune disorders
- Fibroblast Growth Factor Research
- Immune cells in cancer
- Cancer Cells and Metastasis
- Lipid metabolism and biosynthesis
- Mitochondrial Function and Pathology
- Cardiac Ischemia and Reperfusion
- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Phagocytosis and Immune Regulation
- NF-κB Signaling Pathways
- Pharmacological Effects of Natural Compounds
- Receptor Mechanisms and Signaling
- Histone Deacetylase Inhibitors Research
- Autoimmune and Inflammatory Disorders Research
- Liver Diseases and Immunity
Virginia Cancer Institute
2017-2022
VCU Massey Comprehensive Cancer Center
2017-2022
Children's Hospital of Richmond at VCU
2021
Virginia Commonwealth University
2011-2020
University of Mississippi Medical Center
2019
Jackson Memorial Hospital
2019
Universidad Maimónides
2015
Virginia Commonwealth University Medical Center
2002-2006
Georgetown University
2001-2002
Georgetown University Medical Center
2001
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...
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...
Recently, we demonstrated that ceramide kinase, and its product, 1-phosphate (Cer-1-P), were mediators of arachidonic acid released in cells response to interleukin-1β calcium ionophore (Pettus, B. J., Bielawska, A., Spiegel, S., Roddy, P., Hannun, Y. Chalfant, C. E. (2003) J. Biol. Chem. 278, 38206–38213). In this study, demonstrate down-regulation cytosolic phospholipase A2 (cPLA2) using RNA interference technology abolished the ability Cer-1-P induce release A549 cells, demonstrating...
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...
There are two isoforms of sphingosine kinase (SphK) that catalyze the formation 1-phosphate, a potent sphingolipid mediator. Whereas SphK1 stimulates growth and survival, here we show SphK2 enhanced apoptosis in diverse cell types also suppressed cellular proliferation. Apoptosis was preceded by cytochrome c release activation caspase-3. SphK2-induced independent 1-phosphate receptors. Sequence analysis revealed contains 9-amino acid motif similar to present BH3-only proteins, pro-apoptotic...
Sphingosine‐1‐phosphate (S1P) is a potent lysolipid involved in variety of biological responses important for cancer progression. Therefore, we investigated the role sphingosine kinase type 1 (SphK1), enzyme that makes S1P, motility, growth, and chemoresistance MCF‐7 breast cells. Epidermal growth factor (EGF), an progression, activated translocated SphK1 to plasma membrane. was required EGF‐directed motility. Downregulation cells reduced EGF‐ serum‐stimulated enhanced sensitivity...
Sphingosine-1-phosphate (S1P), a ligand for 5 specific receptors, is potent lipid mediator that plays important roles in lymphocyte trafficking and immune responses. S1P produced inside cells therefore must be secreted to exert its effects through these receptors. Spinster 2 (Spns2) one of the cell surface transporters thought secrete S1P. We have shown Spns2 can export endogenous from also dihydro-S1P, which active at all Moreover, Spns2–/– mice decreased levels both phosphorylated...
Transient, reversible blockade of complex I during early reperfusion after ischemia limits cardiac injury. We studied the cardioprotection high dose metformin in cultured cells and mouse hearts via novel mechanism acute downregulation I. The effect on activity was isolated heart mitochondria H9c2 cells. Protection with evaluated at reoxygenation perfused vivo regional reperfusion. Acute, high-dose treatment inhibited ischemia-damaged following hypoxia. Accompanying modulation, decreased...
The process of neurite extension after activation the TrkA tyrosine kinase receptor by nerve growth factor (NGF) involves complex signaling pathways. Stimulation sphingosine 1 (SphK1), enzyme that phosphorylates to form sphingosine-1-phosphate (S1P), is part functional repertoire. In this paper, we report in PC12 cells and dorsal root ganglion neurons, NGF translocates SphK1 plasma membrane differentially activates S1P receptors S1P1 S1P2 a SphK1-dependent manner, as determined with specific...
Sphingosine-1-phosphate (SPP), formed by sphingosine kinase, is the ligand for EDG-1, a GPCR important cell migration and vascular maturation. Here we show that cytoskeletal rearrangements, lamellipodia extensions, motility induced platelet-derived growth factor (PDGF) are abrogated in EDG-1 null fibroblasts. However, appears to be dispensable mitogenicity survival effects, even those its SPP PDGF. Furthermore, PDGF focal adhesion formation activation of FAK, Src, stress-activated protein...
Sphingosine 1-phosphate (S1P), produced by two sphingosine kinase isoenzymes, denoted SphK1 and SphK2, is the ligand for a family of five specific G protein-coupled receptors that regulate cytoskeletal rearrangements cell motility. Whereas many growth factors stimulate SphK1, much less known regulation SphK2. Here we report epidermal factor (EGF) stimulated SphK2 in HEK 293 cells. This first example an agonist-dependent Chemotaxis cells toward EGF was inhibited N,N-dimethylsphingosine,...
Ceramide‐1‐phosphate (C1P) is emerging as a new addition to the family of bioactive sphingolipid metabolites. At low concentrations, C1P enhanced survival NIH 3T3 fibroblasts and A549 lung cancer cells, while at high it reduced induced apoptosis. Apoptosis correlated with degradation pro‐apoptotic ceramide. To examine role endogenous C1P, expression ceramide kinase, enzyme that produces was downregulated, which cellular proliferation, progression into S phase apoptosis by serum starvation....