A5101852593- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Phagocytosis and Immune Regulation
- Cholesterol and Lipid Metabolism
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Drug Transport and Resistance Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Pharmacogenetics and Drug Metabolism
- Lipid metabolism and disorders
- Pancreatic function and diabetes
- MicroRNA in disease regulation
- Biomedical Research and Pathophysiology
- Eicosanoids and Hypertension Pharmacology
- Immune Cell Function and Interaction
- Sarcoma Diagnosis and Treatment
- Ginger and Zingiberaceae research
- Platelet Disorders and Treatments
- Calcium signaling and nucleotide metabolism
- Inflammasome and immune disorders
University of Kentucky
2014-2024
Lexington VA Health Care System
2000-2023
Markey Cancer Center
2022
Albert B. Chandler Hospital
2000-2014
The University of Texas Health Science Center at San Antonio
2006
Emory University
1995-1999
Institute of Biophysics
1992
Bulgarian Academy of Sciences
1992
Recently it has been demonstrated that high density lipoprotein (HDL) binding to scavenger receptors, class B, type I (SR-BI) stimulates endothelial nitric-oxide synthase (eNOS) activity. In the present studies we used a Chinese hamster ovary cell system and human microvascular line confirm HDL eNOS activity in SR-BI-dependent manner. Importantly, have extended these examine mechanism whereby SR-BI eNOS. can be stimulated by an increase intracellular calcium, phosphorylation Akt kinase, or...
Oxidized LDL (oxLDL) have been implicated in diverse biological events leading to the development of atherosclerotic lesions. We previously demonstrated that proliferation cultured vascular smooth muscle cells (SMC) induced by oxLDL is preceded an increase neutral sphingomyelinase activity, sphingomyelin turnover ceramide, and stimulation mitogen-activated protein kinases (Augé, N., Escargueil-Blanc, I., Lajoie-Mazenc, Suc, Andrieu-Abadie, Pieraggi, M. T., Chatelut, M., Thiers, J. C.,...
Interleukin 1β (IL-1β) induces the hydrolysis of sphingomyelin (SM) to ceramide (Cer) in primary cultures rat hepatocytes, and Cer has been proposed play a role down-regulation cytochrome P450 2C11 (CYP2C11) induction α<sub>1</sub>-acid glycoprotein (AGP) by this cytokine (Chen, J., Nikolova-Karakashian, M., Merrill, A. H. & Morgan, E. T. (1995)<i>J. Biol. Chem.</i> 270, 25233–25238). Nonetheless, some features CYP2C11 do not fit simple model as second messenger...
Spatially Fractionated high dose (Grid) Radiation Treatment (SFGRT) involves irradiation of bulky tumors with one high, grid-delivered, 15 Gy followed by multiple consecutive doses 2 each. The goal this study is to determine the effect treatment on serum ceramide content and investigate possible involvement in tumor regression after SFGRT. Serum Secretory SMase (SSMase) were quantified 11 patients before at 24, 48 72 h Gy. Furthermore, LDL particles isolated from their apoptotic ability was...
Sphingolipids are constituents of liver and lipoproteins, but relatively little is known about their synthesis secretion. Incubation rat hepatocytes with [14C]- or [3H]serine labeled the long-chain base backbones mainly ceramide sphingomyelin. Most sphingolipids were associated cells; however, 1-5% (the majority which was ceramide) released into medium as part very low density lipoproteins (VLDL). Since this first report that contain ceramide, isolated from plasma, contents (per mg protein):...
Acid sphingomyelinase plays important roles in ceramide homeostasis, which has been proposed to be linked insulin resistance. To test this association vivo, acid deletion (asm(-/-)) was transferred mice lacking the low density lipoprotein receptor (ldlr(-/-)), and then offsprings were placed on control or modified (enriched saturated fat cholesterol) diets for 10 weeks. The diet caused hypercholesterolemia all genotypes; however, contrast asm(+/+)/ldlr(-/-), sphingomyelinase-deficient...
Abstract Extracellular vesicles (EVs) are shed from the plasma membrane, but regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O in Hela cells stimulated filopodia formation secretion EVs. were small (150 nm) labeled for CD44, indicating they derived filopodia. Filopodia‐derived (sEVs) enriched with sphingolipid ceramide, consistent increased ceramide membrane Ceramide was colocalized neutral sphingomyelinase (nSMase2) acid (ASM), two...
Neutral sphingomyelinase (NSMase) has been proposed to mediate interleukin (IL)-1beta signaling in liver. In this paper, we used adenovirus-mediated gene transfer inducibly express FLAG-tagged mouse NSMase-2 primary rat hepatocytes order further elucidate the molecular nature of NSMase involved. Initial studies confirmed that EST clone these experiments encoded a Mg2+-dependent NSMase. The vitro activity heterologously expressed enzyme was inhibited presence 0.5% Triton or 50 mM EDTA....
Oxidative stress and inflammation are fundamental for the onset of aging appear to be causatively linked. Previously, we reported that hepatocytes from aged rats, compared with young hyperresponsive interleukin-1beta (IL-1beta) stimulation exhibit more potent c-Jun N-terminal kinase (JNK) activation attenuated interleukin-1 receptor-associated kinase-1 (IRAK-1) degradation. An age-related increase in activity neutral sphingomyelinase-2 (NSMase-2), a plasma membrane enzyme, was found...
Acid sphingomyelinase (ASMase) has been proposed to mediate lipopolysaccharide (LPS) signaling in various cell types. This study shows that ASMase is a negative regulator of LPS-induced tumor necrosis factor alpha (TNFalpha) secretion macrophages. ASMase-deficient (asm(-/-)) mice and isolated peritoneal macrophages produce severalfold more TNFalpha than their wild-type (asm(+/+)) counterparts when stimulated with LPS, whereas the addition exogenous ceramides or reduces differences. The...
The role of apoptosis in EtOH-induced liver injury has not been investigated much. Therefore, the question whether is a contributory factor to alcoholic disease remains be answered. purpose this study was characterize apoptotic response murine model alcohol-enhanced lipopolysaccharide (LPS) hepatotoxicity.Mice were fed an alcohol-containing liquid diet for 49 days followed by acute LPS challenge. state judged on basis histological appearance, plasma enzyme activity (alanine:2-oxoglutarate...
Sphingomyelinase (SMase) hydrolyzes membrane sphingomyelin into ceramide, which increases oxidants in nonmuscle cells. Serum SMase activity is elevated sepsis and heart failure, conditions where muscle are increased, maximal force diminished, fatigue accelerated. We tested the hypotheses that exogenous accumulation of ceramide cells, depresses specific unfatigued muscle, accelerates process. also anticipated antioxidant N-acetylcysteine (NAC) would prevent effects on function. studied...
Sphingolipid and oxidant signaling affect glucose uptake, atrophy, force production of skeletal muscle similarly both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. is initiated neutral sphingomyelinase (nSMase), family agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be striated muscle-specific nSMase. The present study tested the hypothesis protein expressed in functions to regulate TNF-stimulated production.We...