BACKGROUND: The roles of sphingosine in various cancers have not been fully investigated. Our aim was to identify the relationship between serum sphingosine and the risk of hepatocellular carcinoma (HCC). METHODS: Serum sphingosine in 34 normal people and 73 HCC patients were reviewed retrospectively. Receiver operating characteristic curve analysis was performed to determine the cut-off values of sphingosine in the serum. Chi-square test, t test and regression analysis were used to test the association between serum sphingosine and individual clinicopathologic parameters. RESULTS: Serum sphingosine was higher in HCC patients (155.91±331.5 ng/mL) with normal persons as the control (30.92±29.4 ng/mL). The sphingosine threshold according to ROC curve was set at 22.5 ng/mL with a sensitivity of 74%, and a specificity of 55.9%. Meanwhile, sphingosine in HCC patients with abnormal albumin was significantly higher than that in patients with normal albumin (t=2.452, P=0.019). When HCC patients were divided into two groups serum sphingosine was negatively associated with albumin in HCC patients (χ2=4.469, P=0.035). Moreover, the logistic regression analysis showed that large tumor size (P=0.018, OR=0.13) and a low albumin (P=0.005, OR=8.856) were two independent risk factors for serum sphingosine upregulation. High AFP coupled with high serum sphingosine, high sphingosine and high AFP respectively were found in 91.2%, 75.4%, 73% of the HCC patients. CONCLUSIONS: These results suggest that serum sphingosine could be treated as a marker for the risk of HCC. AFP and sphingosine in the serum could be used together for HCC diagnosis.

• Klíčová slova
• HCC, albumin, serum sphingolipid,
• MeSH
• alfa-fetoproteiny metabolismus   MeSH
• hepatocelulární karcinom krev   komplikace   diagnóza   patologie   MeSH
• jaterní cirhóza krev   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetné primární nádory krev   komplikace   diagnóza   MeSH
• nádory jater krev   komplikace   diagnóza   patologie   MeSH
• riziko MeSH
• ROC křivka MeSH
• sérový albumin metabolismus   MeSH
• sfingosin krev   MeSH
• studie případů a kontrol MeSH
• tumor burden MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-fetoproteiny MeSH
• sérový albumin MeSH
• sfingosin MeSH

The systemic anaphylactic reaction is a life-threatening allergic response initiated by activated mast cells. Sphingolipids are an essential player in the development and attenuation of this response. De novo synthesis of sphingolipids in mammalian cells is inhibited by the family of three ORMDL proteins (ORMDL1, 2, and 3). However, the cell and tissue-specific functions of ORMDL proteins in mast cell signaling are poorly understood. This study aimed to determine cross-talk of ORMDL2 and ORMDL3 proteins in IgE-mediated responses. To this end, we prepared mice with whole-body knockout (KO) of Ormdl2 and/or Ormdl3 genes and studied their role in mast cell-dependent activation events in vitro and in vivo. We found that the absence of ORMDL3 in bone marrow-derived mast cells (BMMCs) increased the levels of cellular sphingolipids. Such an increase was further raised by simultaneous ORMDL2 deficiency, which alone had no effect on sphingolipid levels. Cells with double ORMDL2 and ORMDL3 KO exhibited increased intracellular levels of sphingosine-1-phosphate (S1P). Furthermore, we found that concurrent ORMDL2 and ORMDL3 deficiency increased IκB-α phosphorylation, degranulation, and production of IL-4, IL-6, and TNF-α cytokines in antigen-activated mast cells. Interestingly, the chemotaxis towards antigen was increased in all mutant cell types analyzed. Experiments in vivo showed that passive cutaneous anaphylaxis (PCA), which is initiated by mast cell activation, was increased only in ORMDL2,3 double KO mice, supporting our in vitro observations with mast cells. On the other hand, ORMDL3 KO and ORMDL2,3 double KO mice showed faster recovery from passive systemic anaphylaxis, which could be mediated by increased levels of blood S1P presented in such mice. Our findings demonstrate that Ormdl2 deficiency potentiates the ORMDL3-dependent changes in mast cell signaling.

• Klíčová slova
• FcϵRI, ORMDL family, mast cells, passive cutaneous anaphylactic reaction, passive systemic anaphylaxis, sphingolipids, sphingosine-1-phosphate,
• MeSH
• anafylaxe etiologie   metabolismus   MeSH
• biologické markery MeSH
• chemotaxe imunologie   MeSH
• cytokiny metabolismus   MeSH
• exprese genu MeSH
• lysofosfolipidy krev   metabolismus   MeSH
• mastocyty imunologie   metabolismus   MeSH
• membránové proteiny chemie   nedostatek   genetika   metabolismus   MeSH
• multigenová rodina MeSH
• myši knockoutované MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• pasivní kožní anafylaxe genetika   imunologie   MeSH
• sekvence aminokyselin MeSH
• sfingolipidy krev   metabolismus   MeSH
• sfingosin analogy a deriváty   krev   metabolismus   MeSH
• signální transdukce * MeSH
• vápník metabolismus   MeSH
• vápníková signalizace MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• lysofosfolipidy MeSH
• membránové proteiny MeSH
• ORMDL3 protein, mouse MeSH Prohlížeč
• sfingolipidy MeSH
• sfingosin MeSH
• sphingosine 1-phosphate MeSH Prohlížeč
• vápník MeSH

Acid sphingomyelinase deficiency (ASMd, Niemann-Pick disease A/B) and Niemann-Pick type C disease (NPC) share core clinical symptoms. Initial diagnostic discrimination of these two rare lysosomal storage diseases is thus difficult. As sphingomyelin accumulates in ASMd as well as NPC, lysosphingomyelin (sphingosylphosphorylcholine) and its m/z 509 analog were suggested as biomarkers for both diseases. Herein we present results of simultaneous LC-ESI-MS/MS measurements of lysosphingomyelin and lysosphingomyelin 509 in plasma and dried blood spots (DBS) collected from ASMd and NPC patients and suggest that the plasma but not DBS levels of the two analytes allow differential biochemical screening of ASMd and NPC.

• Klíčová slova
• Lysosphingomyelin, Mass spectrometry, Niemann-Pick A/B, Niemann-Pick C, Screening, Sphingosylphosphorylcholine,
• MeSH
• biologické markery krev   MeSH
• chromatografie kapalinová metody   MeSH
• fosforylcholin analogy a deriváty   krev   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• lidé MeSH
• Niemannova-Pickova nemoc typu A krev   diagnóza   MeSH
• Niemannova-Pickova nemoc typu B krev   diagnóza   MeSH
• Niemannova-Pickova nemoc typu C krev   diagnóza   MeSH
• sfingosin analogy a deriváty   krev   MeSH
• studie případů a kontrol MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• test suché kapky krve metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• fosforylcholin MeSH
• sfingosin MeSH
• sphingosine phosphorylcholine MeSH Prohlížeč