Sphingosine Kinase 2 Triggers Cell Death

2003 ◽  
Vol 2003 (204) ◽  
pp. tw407-tw407
Keyword(s):  
Cell Death ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 2

Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells

Blood ◽  
2010 ◽  
Vol 115 (17) ◽  
pp. 3531-3540 ◽  
Author(s):  
Andreas Weigert ◽  
Sarah Cremer ◽  
Martina Victoria Schmidt ◽  
Andreas von Knethen ◽  
Carlo Angioni ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cell ◽  
Apoptotic Cell ◽  
Sphingosine Kinase ◽  
Relevant Information ◽  
Lipid Mediator ◽  
Apoptotic Cells ◽  
Dependent Manner ◽  
Sphingosine Kinase 2 ◽  
Caspase 1

Abstract Execution of physiologic cell death known as apoptosis is tightly regulated and transfers immunologically relevant information. This ensures efficient clearance of dying cells and shapes the phenotype of their “captors” toward anti-inflammatory. Here, we identify a mechanism of sphingosine-1-phosphate production by apoptotic cells. During cell death, sphingosine kinase 2 (SphK2) is cleaved at its N-terminus in a caspase-1–dependent manner. Thereupon, a truncated but enzymatically active fragment of SphK2 is released from cells. This step is coupled to phosphatidylserine exposure, which is a hallmark of apoptosis and a crucial signal for phagocyte/apoptotic cell interaction. Our data link signaling events during apoptosis to the extracellular production of a lipid mediator that affects immune cell attraction and activation.

Sphingosine kinase-2 Inhibitor ABC294640 Enhances Doxorubicin-Induced Apoptosis of NSCLC Cells via Altering Survivin Expression

Drug Research ◽  
2017 ◽  
Vol 68 (01) ◽  
pp. 45-53 ◽  
Author(s):  
Hasanifard Leili ◽  
Samadi Nasser ◽  
Rashtchizadeh Nadereh ◽  
Dastmalchi Siavoush ◽  
Karimi Pouran
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Combined Treatment ◽  
Survivin Expression ◽  
Sphingosine Kinase ◽  
Dapi Staining ◽  
Sphingosine Kinase 2 ◽  
Gene And Protein Expression ◽  
Proliferation And Apoptosis ◽  
Induced Apoptosis

Abstract Background There is an urgent need to improve efficacy of chemotherapeutics to overcome resistance in cancer treatment. Sphingosine kinase-2 (SphK2) a key regulator of sphingolipid signaling has been rationalized as an important therapeutic target. We evaluated the role of SphK2 in doxorubicin (DOX)-induced apoptosis of NSCLC cells via altering c-FLIPS, MCL-1 and survivin expressions in order to overcome chemoresistance. Methods Proliferation and apoptosis were evaluated by MTT assay and DAPI staining, respectively. Cell population in each phase of cell cycle was determined by flow cytometric assay. Gene and protein expression levels were examined by quantitative RT-PCR and western blot analysis, respectively. Results Phorbol myristate acetate (PMA), a SphK2 stimulator, decreased cell death induced by IC50 of DOX (1.1 µM) to around 70% (p<0.01). Cell cycle analysis revealed a significant accumulation of the cells in S phase with a marked decrease in sub G1 phase when we incubated the cells with combined treatment of PMA and DOX (p<0.05). Adding ABC294640 (40 µM), a SphK2 inhibitor, significantly abolished PMA effect on cell survival (p<0.01). Survivin expression was significantly diminished by applying ABC294640 either alone or in DOX treated cells followed by increase in cell death (p<0.05), however, there was no significant change in MCL-1 expression by ABC294640 either alone or in DOX treated cells (p=0.16) and (p=0.06), respectively. Conclusion Identifying cancer patients with high SphK2 expression and then inhibiting of SphK2 activity can be considered as an important strategy to increase the efficacy of DOX in the induction of apoptosis.

scholarly journals Sphingosine Kinase 2 Inhibitor Accelerates Fas-Mediated Cell Death Progression in A20/2J Cells

2008 ◽  
Vol 1 ◽  
pp. 22-27 ◽  
Author(s):  
Miki Hara-Yokoyama ◽  
Kazue Terasawa ◽  
Akio Kihara ◽  
Jin-Wook Kim ◽  
Chan-Seo Park ◽  
...  
Keyword(s):  
Cell Death ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 2

Apoptotic cell extrusion depends on single-cell synthesis of sphingosine-1-phosphate by sphingosine kinase 2

2021 ◽  
Vol 1866 (4) ◽  
pp. 158888
Author(s):  
Bruno Jaime Santacreu ◽  
Daniela Judith Romero ◽  
Lucila Gisele Pescio ◽  
Estefanía Tarallo ◽  
Norma Beatriz Sterin-Speziale ◽  
...  
Keyword(s):  
Single Cell ◽  
Apoptotic Cell ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 2 ◽  
Sphingosine 1 Phosphate ◽  
Cell Synthesis ◽  
Cell Extrusion

scholarly journals Reduced sphingosine kinase 1 activity in dengue virus type-2 infected cells can be mediated by the 3′ untranslated region of dengue virus type-2 RNA

2013 ◽  
Vol 94 (11) ◽  
pp. 2437-2448 ◽  
Author(s):  
J. M. Carr ◽  
T. Kua ◽  
J. N. Clarke ◽  
J. K Calvert ◽  
J. R. Zebol ◽  
...  
Keyword(s):  
Cell Death ◽  
Dengue Virus ◽  
Virus Type ◽  
Elongation Factor ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Diarrhea Virus ◽  
Infected Cells ◽  
Dengue Virus Type 2

Sphingosine kinase 1 (SphK1) is a lipid kinase with important roles including regulation of cell survival. We have previously shown reduced SphK1 activity in cells with an established dengue virus type-2 (DENV-2) infection. In this study, we examined the effect of alterations in SphK1 activity on DENV-2 replication and cell death and determined the mechanisms of the reduction in SphK1 activity. Chemical inhibition or overexpression of SphK1 after established DENV-2 infection had no effect on infectious DENV-2 production, although inhibition of SphK1 resulted in enhanced DENV-2-induced cell death. Reduced SphK1 activity was observed in multiple cell types, regardless of the ability of DENV-2 infection to be cytopathic, and was mediated by a post-translational mechanism. Unlike bovine viral diarrhea virus, where SphK1 activity is decreased by the NS3 protein, SphK1 activity was not affected by DENV-2 NS3 but, instead, was reduced by expression of the terminal 396 bases of the 3′ UTR of DENV-2 RNA. We have previously shown that eukaryotic elongation factor 1A (eEF1A) is a direct activator of SphK1 and here DENV-2 RNA co-localized and co-precipitated with eEF1A from infected cells. We propose that the reduction in SphK1 activity late in DENV-2-infected cells is a consequence of DENV-2 out-competing SphK1 for eEF1A binding and hijacking cellular eEF1A for its own replication strategy, rather than a specific host or virus-induced change in SphK1 to modulate viral replication. Nonetheless, reduced SphK1 activity may have important consequences for survival or death of the infected cell.

scholarly journals ABC294640, A Novel Sphingosine Kinase 2 Inhibitor, Induces Oncogenic Virus–Infected Cell Autophagic Death and Represses Tumor Growth

2017 ◽  
Vol 16 (12) ◽  
pp. 2724-2734 ◽  
Author(s):  
Lu Dai ◽  
Aiping Bai ◽  
Charles D. Smith ◽  
Paulo C. Rodriguez ◽  
Fangyou Yu ◽  
...  
Keyword(s):  
Infected Cell ◽  
Tumor Growth ◽  
Sphingosine Kinase ◽  
Oncogenic Virus ◽  
Virus Infected Cell ◽  
Sphingosine Kinase 2

Islet Co-Expression of CD133 and ABCB5 in Human Retinoblastoma Specimens

2021 ◽  
Author(s):  
Marco Zschoche ◽  
Sergej Skosyrski ◽  
Neele Babst ◽  
Mahdy Ranjbar ◽  
Felix Rommel ◽  
...  
Keyword(s):  
Treatment Resistance ◽  
Sphingosine Kinase ◽  
Immunohistochemical Analysis ◽  
Pcr Analysis ◽  
Sphingosine Kinase 1 ◽  
Rt Pcr ◽  
Beam Radiation ◽  
Sphingosine Kinase 2 ◽  
Human Retinoblastoma

Abstract Background The role of CD133 und ABCB5 is discussed in treatment resistance in several types of cancer. The objective of this study was to evaluate whether CD133+/ABCB5+ colocalization differs in untreated, in beam radiation treated, and in chemotherapy treated retinoblastoma specimens. Additionally, CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 gene expression was analyzed in WERI-RB1 (WERI RB1) and etoposide-resistant WERI RB1 subclones (WERI ETOR). Methods Active human untreated retinoblastoma specimens (n = 12), active human retinoblastoma specimens pretreated with beam radiation before enucleation (n = 8), and active human retinoblastoma specimens pretreated with chemotherapy before enucleation (n = 7) were investigated for localization and expression of CD133 and ABCB5 by immunohistochemistry. Only specimens with IIRC D, but not E, were included in this study. Furthermore, WERI RB1 and WERI ETOR cell lines were analyzed for CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 by the real-time polymerase chain reaction (RT-PCR). Results Immunohistochemical analysis revealed the same amount of CD133+/ABCB5+ colocalization islets in untreated and treated human retinoblastoma specimens. Quantitative RT-PCR analysis showed a statistically significant upregulation of CD133 in WERI ETOR (p = 0.002). No ABCB5 expression was detected in WERI RB1 and WERI ETOR. On the other hand, SPHK1 (p = 0.0027) and SPHK2 (p = 0.017) showed significant downregulation in WERI ETOR compared to WERI RB1. Conclusions CD133+/ABCB5+ co-localization islets were noted in untreated and treated human retinoblastoma specimens. Therefore, we assume that CD133+/ABCB5+ islets might play a role in retinoblastoma genesis, but not in retinoblastoma treatment resistance.

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