Sphingosine Kinase Inhibition Enhances Dimerization of Calreticulin at the Cell Surface in Mitoxantrone-Induced Immunogenic Cell Death
| Autor: | Asvelt J. Nduwumwami, Jong K. Yun, Jeremy A. Hengst |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Ceramide biology Sphingosine Chemistry Cell Membrane Sphingosine kinase Sphingolipid Phosphotransferases (Alcohol Group Acceptor) chemistry.chemical_compound Membrane Microdomains biology.protein Molecular Medicine Immunogenic cell death Sphingosine-1-phosphate Mitoxantrone Calreticulin Cellular localization |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 378:300-310 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.121.000629 |
| Popis: | Agents that induce immunogenic cell death (ICD) alter the cellular localization of calreticulin (CRT) causing it to become cell surface exposed within the plasma membrane lipid raft microdomain (ectoCRT) where it serves as a damage associated molecular pattern that elicits an antitumor immune response. We have identified the sphingolipid metabolic pathway as an integral component of the process of ectoCRT exposure. Inhibition of the sphingosine kinases (SphKs) enhances mitoxantrone-induced production of hallmarks of ICD including ectoCRT production, with an absolute mean difference of 40 MFI (95% CI: 19 to 62; P=0.0014) and 1.3 fold increase of ATP secretion with an absolute mean difference of 87 RLU (95% CI: 55 to 120; P |
| Databáze: | OpenAIRE |
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