Ceramide‐rich platforms in transmembrane signaling

Stancevic, Branka; Kolesnick, Richard

doi:10.1016/j.febslet.2010.02.026

Cited by 251 publications

(208 citation statements)

References 163 publications

(209 reference statements)

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“…Sphingolipids such as ceramide are currently recognized as vital regulators of many biological processes (1)(2)(3)(4), and the levels and turnover of these bioactive sphingolipids are regulated by several enzymes. The hydrolysis of sphingomyelin (SM) 2 is a major pathway for ceramide production, and this reaction is catalyzed by the sphingomyelinases (SMases).…”

mentioning

confidence: 99%

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Identification of Novel Anionic Phospholipid Binding Domains in Neutral Sphingomyelinase 2 with Selective Binding Preference

Clarke

Matmati

et al. 2011

Journal of Biological Chemistry

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Sphingolipids such as ceramide are recognized as vital regulators of many biological processes. Neutral sphingomyelinase 2 (nSMase2) is one of the key enzymes regulating ceramide production. It was previously shown that the enzymatic activity of nSMase2 was dependent on anionic phospholipids (APLs). In this study, the structural requirements for APL-selective binding of nSMase2 were determined and characterized. Using lipidprotein overlay assays, nSMase2 interacted specifically and directly with several APLs, including phosphatidylserine and phosphatidic acid. Lipid-protein binding studies of deletion mutants identified two discrete APL binding domains in the N terminus of nSMase2. Further, mutagenesis experiments pinpointed the core sequences and major cationic amino acids in the domains that are necessary for the cooperative activation of nSMase2 by APLs. The first domain included the first aminoterminal hydrophobic segment and Arg-33, which were essential for nSMase2 to interact with APLs. The second binding domain was comprised of the second hydrophobic segment and Arg-92 and Arg-93. Moreover, mutation of one or both domains decreased APL binding and APL-dependent catalytic activity of nSMase2. Further, mutation of both domains in nSMase2 reduced its plasma membrane localization. Finally, these binding domains are also important for the capability of nSMase2 to rescue the defects of yeast lacking the nSMase homologue, ISC1. In conclusion, these data have identified the APL binding domains of nSMase2 for the first time. The analysis of interactions between nSMase2 and APLs will contribute to our understanding of signaling pathways mediated by sphingolipid metabolites.Sphingolipids such as ceramide are currently recognized as vital regulators of many biological processes (1-4), and the levels and turnover of these bioactive sphingolipids are regulated by several enzymes.

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mentioning

confidence: 99%

“…The hydrolysis of sphingomyelin (SM) 2 is a major pathway for ceramide production, and this reaction is catalyzed by the sphingomyelinases (SMases). Currently, six different SMases have been identified and grouped based upon their catalytic pH optima, including an acid SMase, an alkaline SMase and four neutral SMases (N-SMases) (5)(6)(7)(8).…”

mentioning

confidence: 99%

Identification of Novel Anionic Phospholipid Binding Domains in Neutral Sphingomyelinase 2 with Selective Binding Preference

Clarke

Matmati

et al. 2011

Journal of Biological Chemistry

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“…aSMase regulates anti-DENV NS1 Ab-induced ceramide generation, NO production, and apoptosis Ceramide can be generated from sphingomyelin hydrolysis by aSMase (41,43,46,47). Interestingly, after anti-DENV NS1 stimulation, the accumulation of aSMase could be detected by confocal microscopic observation (Fig.…”

Section: Anti-denv Ns1 Treatment Induces Ceramide Generationmentioning

confidence: 94%

“…The formation of lipid rafts, the membrane microdomains that are enriched in cholesterol and glycosphingolipids, play an important role in cellular signaling in response to various stimuli (31)(32)(33)(34)(35). Ceramide, which is enriched in lipid rafts, acts as a second messenger of multiple extracellular stimuli in cell survival, inflammation, and apoptotic cell death (36)(37)(38)(39)(40)(41). We investigated the formation of raft structure and the generation of cellular ceramide after binding of anti-DENV NS1 Abs to endothelial cells.…”

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confidence: 99%

Anti–Dengue Virus Nonstructural Protein 1 Antibodies Cause NO-Mediated Endothelial Cell Apoptosis via Ceramide-Regulated Glycogen Synthase Kinase-3β and NF-κB Activation

Chen

Lin

Wan

et al. 2013

The Journal of Immunology

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Immunopathogenetic mechanisms of dengue virus (DENV) infection are involved in hemorrhagic syndrome resulting from thrombocytopenia, coagulopathy, and vasculopathy. We have proposed a mechanism of molecular mimicry in which Abs against DENV nonstructural protein 1 (NS1) cross-react with human endothelial cells and cause NF-κB–regulated immune activation and NO-mediated apoptosis. However, the signaling pathway leading to NF-κB activation after the binding of anti-DENV NS1 Abs to endothelial cells is unresolved. In this study, we found that anti-DENV NS1 Abs caused the formation of lipid raftlike structures, and that disrupting lipid raft formation by methyl-β-cyclodextrin decreased NO production and apoptosis. Treatment with anti-DENV NS1 Abs elevated ceramide generation in lipid rafts. Pharmacological inhibition of acid sphingomyelinase (aSMase) decreased anti-DENV NS1 Ab-mediated ceramide and NO production, as well as apoptosis. Exogenous ceramide treatment induced biogenesis of inducible NO synthase (iNOS)/NO and apoptosis through an NF-κB–regulated manner. Furthermore, activation of glycogen synthase kinase-3β (GSK-3β) was required for ceramide-induced NF-κB activation and iNOS expression. Notably, anti-DENV NS1 Abs caused GSK-3β–mediated NF-κB activation and iNOS expression, which were regulated by aSMase. Moreover, pharmacological inhibition of GSK-3β reduced hepatic endothelial cell apoptosis in mice passively administered anti-DENV NS1 Abs. These results suggest that anti-DENV NS1 Abs bind to the endothelial cell membrane and cause NO production and apoptosis via a mechanism involving the aSMase/ceramide/GSK-3β/NF-κB/iNOS/NO signaling pathway.

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“…In previous studies, factors of inflammation, including TNF-α, ROS, LPS, amyloid-β, IL-1β, and LDL, stimulated SMase activation activity, which then produced ceramide and initiated ceramide signal pathways to transfer death signaling [25][26][27]. This study evaluated the effects of LMG on bacterial SMase activity in vitro.…”

Section: Lmg Inhibited Smase Activitymentioning

confidence: 99%

β-Glucan Contents and Anti-wrinkling Effects of Brown Rice <i>Phellinus linteus</i> Mycelium Extracts Fermented with Lactobacillus plantarum

Kim¹,

Ahn²,

Kwon³

et al. 2016

Asian J Beauty Cosmetol

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The major cell wall constituent of Ganoderma lucidum (G. lucidum) is β-1,3-glucan. This study examined the polysaccharide from the residues of alkaline-extracted fruiting bodies using high-performance anion-exchange chromatography (HPAEC), and it employed nuclear magnetic resonance (NMR) and mass spectrometry (MS) to confirm the structures. We have successfully isolated low-molecular-weight β-1,3-glucan (LMG), in high yields, from the waste residue of extracted fruiting bodies of G. lucidum. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay evaluated the capability of LMG to suppress H 2 O 2 -induced cell death in RAW264.7 cells, identifying that LMG protected cells from H 2 O 2 -induced damage. LMG treatment decreased H 2 O 2 -induced intracellular reactive oxygen species (ROS) production. LMG also influenced sphingomyelinase (SMase) activity, stimulated by cell death to induce ceramide formation, and then increase cell ROS production. Estimation of the activities of neutral and acid SMases in vitro showed that LMG suppressed the activities of both neutral and acid SMases in a concentrationdependent manner. These results suggest that LMG, a water-soluble β-1,3-glucan recycled from extracted residue of G. lucidum, possesses antioxidant capability against H 2 O 2 -induced cell death by attenuating intracellular ROS and inhibiting SMase activity.

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Ceramide‐rich platforms in transmembrane signaling

Cited by 251 publications

References 163 publications

Identification of Novel Anionic Phospholipid Binding Domains in Neutral Sphingomyelinase 2 with Selective Binding Preference

Identification of Novel Anionic Phospholipid Binding Domains in Neutral Sphingomyelinase 2 with Selective Binding Preference

Anti–Dengue Virus Nonstructural Protein 1 Antibodies Cause NO-Mediated Endothelial Cell Apoptosis via Ceramide-Regulated Glycogen Synthase Kinase-3β and NF-κB Activation

β-Glucan Contents and Anti-wrinkling Effects of Brown Rice <i>Phellinus linteus</i> Mycelium Extracts Fermented with Lactobacillus plantarum

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