Involvement of the acid sphingomyelinase pathway in uva-induced apoptosis.
AuthorsZhang Y, Mattjus P, Schmid PC, Dong Z, Zhong S, Ma WY, Brown RE, Bode AM, Schmid HH, Dong Z
JournalJ Biol Chem
PubMed ID11278294
'The sphingomyelin-ceramide pathway is an evolutionarily conserved ubiquitous signal transduction system that regulates many cell functions including apoptosis. Sphingomyelin (SM) is hydrolyzed to ceramide by different sphingomyelinases. Ceramide serves as a second messenger in mediating cellular effects of cytokines and stress. In this study, we find that acid sphingomyelinase (SMase) ... More
Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse.
AuthorsPassini MA, Bu J, Fidler JA, Ziegler RJ, Foley JW, Dodge JC, Yang WW, Clarke J, Taksir TV, Griffiths DA, Zhao MA, O'Riordan CR, Schuchman EH, Shihabuddin LS, Cheng SH
JournalProc Natl Acad Sci U S A
PubMed ID17517638
'Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation of undegraded lipids in cells of the viscera and CNS. In this study, we tested the effect of combination brain and systemic injections of recombinant adeno-associated viral vectors encoding human ASM (hASM) ... More
Protection from high fat diet-induced increase in ceramide in mice lacking plasminogen activator inhibitor 1.
AuthorsShah C, Yang G, Lee I, Bielawski J, Hannun YA, Samad F,
JournalJ Biol Chem
PubMed ID18359942
'Obesity increases the risk for metabolic and cardiovascular disease, and adipose tissue plays a central role in this process. Ceramide, the key intermediate of sphingolipid metabolism, also contributes to obesity-related disorders. We show that a high fat diet increased ceramide levels in the adipose tissues and plasma in C57BL/6J mice ... More
Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid.
AuthorsRamu Y, Xu Y, Shin HG, Lu Z,
Journal
PubMed ID25313718
'Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause recurring bacterial infection in CF patients'' lungs. However, the severity of CF lung disease correlates poorly with genotype. Antibiotic treatment helps dramatically prolong patients'' life. The lung disease generally determines prognosis and causes most morbidity and mortality; early control of ... More
Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice.
AuthorsPetrache I, Natarajan V, Zhen L, Medler TR, Richter AT, Cho C, Hubbard WC, Berdyshev EV, Tuder RM
JournalNat Med
PubMed ID15852018
'Alveolar cell apoptosis is involved in the pathogenesis of emphysema, a prevalent disease primarily caused by cigarette smoking. We report that ceramide, a second messenger lipid, is a crucial mediator of alveolar destruction in emphysema. Inhibition of enzymes controlling de novo ceramide synthesis prevented alveolar cell apoptosis, oxidative stress and ... More
Purification and functional characterization of insecticidal sphingomyelinase C produced by Bacillus cereus.
AuthorsNishiwaki H, Ito K, Otsuki K, Yamamoto H, Komai K, Matsuda K
JournalEur J Biochem
PubMed ID14728687
'Bacillus cereus isolated from the larvae of Myrmeleon bore was found to secrete proteins that paralyze and kill German cockroaches, Blattela germanica, when injected. One of these active proteins was purified from the culture broth of B. cereus using anion-exchange and gel-filtration chromatography. The purified toxin, with a molecular mass ... More
Characterizing the sphingomyelinase pathway triggered by PRIMA-1 derivatives in lung cancer cells with differing p53 status.
AuthorsSoans E, Evans SC, Cipolla C, Fernandes E,
Journal
PubMed ID24982331
Derivatives of PRIMA-1 compound, 8a and 8b have been shown to increase cytotoxicity in lung cancer cells through sphingomyelinase pathways in IR and 8a or 8b co-treated lung cancer cells. The goal of the present study was to further elaborate the molecular mechanism of 8a- or 8b-treated lung cancer cells ... More
Lipid-modifying enzymes in human tear fluid and corneal epithelial stress response.
AuthorsRobciuc A, Rantamäki AH, Jauhiainen M, Holopainen JM,
Journal
PubMed ID24302584
Since homeostasis at the ocular surface requires a delicate balance between numerous factors, and the external environment contributes as an unpredictable component, we aimed to understand the role that various lipids and their regulators have in the complex process that maintains a healthy corneal surface. Through basic proteomics, we tested ... More
Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin.
AuthorsGrimm MO, Grimm HS, Pätzold AJ, Zinser EG, Halonen R, Duering M, Tschäpe JA, De Strooper B, Müller U, Shen J, Hartmann T
JournalNat Cell Biol
PubMed ID16227967
Amyloid beta peptide (Abeta) has a key role in the pathological process of Alzheimer's disease (AD), but the physiological function of Abeta and of the amyloid precursor protein (APP) is unknown. Recently, it was shown that APP processing is sensitive to cholesterol and other lipids. Hydroxymethylglutaryl-CoA reductase (HMGR) and sphingomyelinases ... More
Cholesterol depletion suppresses the translational diffusion of class II major histocompatibility complex proteins in the plasma membrane.
AuthorsVrljic M, Nishimura SY, Moerner WE, McConnell HM
JournalBiophys J
PubMed ID15516525
Glycosylphosphatidylinositol (GPI)-linked and native major histocompatibility complex class II I-E(k) were used as probes to determine the effect of varying cholesterol concentration on the mobility of proteins in the plasma membrane. These proteins were imaged in Chinese hamster ovary cells using single-molecule fluorescence microscopy. Observed diffusion coefficients of both native ... More
Regulation of the activity and fatty acid specificity of lecithin-cholesterol acyltransferase by sphingomyelin and its metabolites, ceramide and ceramide phosphate.
AuthorsSubbaiah PV, Horvath P, Achar SB
JournalBiochemistry
PubMed ID16605271
Sphingomyelin (SM), the second most abundant phospholipid in plasma lipoproteins, was previously shown to be a physiological inhibitor of the lecithin-cholesterol acyltransferase (LCAT) reaction. In this study, we investigated the effects of its metabolites, ceramide and ceramide phosphate, on the activity and fatty acid specificity of LCAT in vitro. Treatment ... More
The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells.
AuthorsLakkaraju A, Finnemann SC, Rodriguez-Boulan E
JournalProc Natl Acad Sci U S A
PubMed ID17578916
Proteins involved in cholesterol trafficking are known to contribute to the pathogenesis of atherosclerosis and Alzheimer's disease. Allelic variants in the cholesterol transporters apolipoprotein E and ATP-binding cassette protein A1 (ABCA1) have recently been associated with susceptibility to age-related macular degeneration (AMD). Histopathological analyses of eyes with AMD demonstrate the ... More