Signalling Effects Induced by Acid Ceramidase in Human Epithelial Or Leukemic Cell Lines

Baduva, Käthe; Büchter, Lara; Kreyenkamp, Katja; Westphal, Linnea; Wilker, Barbara; Kohnen, Marcus; Schuchman, Edward H.; Edwards, Michael J.; Becker, Katrin Anne; Gulbins, Erich; Carpinteiro, Alexander

doi:10.33594/000000074

Cited by 3 publications

(1 citation statement)

References 31 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, exogenous application of acid ceramidase was found to cause Akt kinase activation in Jurkat cells, and, however, affected their expansion. The latter was suggested to relate to the inability of the added ceramidase to promote activation of sphingosine kinase and, thereby, production of S1P in this system (Baduva et al, 2019). The ability of this particular bioactive sphingolipid to substantially regulate survival, trafficking, and activity of immune cells including T cells is well established, and with FTY720, a drug targeting S1P activity is in clinical use.…”

Section: Sphingomyelinases Take Part In But Are Not the Sole Players mentioning

confidence: 99%

Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen

Avota

Lira

Schneider‐Schaulies

2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Sphingolipids are major components of cellular membranes, and at steady-state level, their metabolic fluxes are tightly controlled. On challenge by external signals, they undergo rapid turnover, which substantially affects the biophysical properties of membrane lipid and protein compartments and, consequently, signaling and morphodynamics. In T cells, external cues translate into formation of membrane microdomains where proximal signaling platforms essential for metabolic reprograming and cytoskeletal reorganization are organized. This review will focus on sphingomyelinases, which mediate sphingomyelin breakdown and ensuing ceramide release that have been implicated in T-cell viability and function. Acting at the sphingomyelin pool at the extrafacial or cytosolic leaflet of cellular membranes, acid and neutral sphingomyelinases organize ceramide-enriched membrane microdomains that regulate T-cell homeostatic activity and, upon stimulation, compartmentalize receptors, membrane proximal signaling complexes, and cytoskeletal dynamics as essential for initiating T-cell motility and interaction with endothelia and antigen-presenting cells. Prominent examples to be discussed in this review include death receptor family members, integrins, CD3, and CD28 and their associated signalosomes. Progress made with regard to experimental tools has greatly aided our understanding of the role of bioactive sphingolipids in T-cell biology at a molecular level and of targets explored by a model pathogen (measles virus) to specifically interfere with their physiological activity.

show abstract

Section: Sphingomyelinases Take Part In But Are Not the Sole Players mentioning

confidence: 99%

Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen

Avota

Lira

Schneider‐Schaulies

2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

Targeting nanocomposites with anti-oxidative/inflammatory/angiogenic activities for synergistically alleviating macular degeneration

Luo

Jian

Harroun

et al. 2021

Applied Materials Today

View full text Add to dashboard Cite

Cell-intrinsic ceramides determine T cell function during melanoma progression

Hose

Günther

Naser

et al. 2022

Preprint

View full text Add to dashboard Cite

Acid sphingomyelinase (Asm) and acid ceramidase (Ac) are parts of the sphingolipid metabolism. Asm hydrolyzes sphingomyelin to ceramide, which is further metabolized to sphingosine by Ac. Ceramide generates ceramide-enriched platforms that are involved in receptor clustering within cellular membranes. However, the impact of cell intrinsic ceramide on T cell function is not well characterized. By using T cell-specific Asm- or Ac-deficient mice, with reduced or elevated ceramide levels in T cells, we identified ceramide to play a crucial role in T cell function in vitro and in vivo. T cell specific ablation of Asm in Asmflox/flox/CD4cre mice resulted in enhanced tumor progression associated with impaired T cell responses, whereas Acflox/flox/CD4cre mice showed reduced tumor growth rates and elevated T cell activation compared to the respective controls upon tumor transplantation. Further in vitro analysis revealed that decreased ceramide content supports CD4+ regulatory T cell differentiation and interferes with cytotoxic activity of CD8+ T cells. In contrast, elevated ceramide concentration in CD8+ T cells from Acflox/flox/CD4cre mice was associated with enhanced cytotoxic activity. Strikingly, ceramide co-localized with the T cell receptor (TCR) and CD3 in the membrane of stimulated T cells and phosphorylation of TCR signaling molecules was elevated in Ac-deficient T cells. Hence, our results indicate that modulation of ceramide levels, by interfering with the Asm or Ac activity has an effect on T cell differentiation and function and might therefore represent a novel therapeutic strategy for the treatment of T cell-dependent diseases such as tumorigenesis.

show abstract

Signalling Effects Induced by Acid Ceramidase in Human Epithelial Or Leukemic Cell Lines

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 3 publications

References 31 publications

Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen

Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen

Targeting nanocomposites with anti-oxidative/inflammatory/angiogenic activities for synergistically alleviating macular degeneration

Cell-intrinsic ceramides determine T cell function during melanoma progression

Contact Info

Product

Resources

About