High Dose C6 Ceramide-Induced Response in Embryonic Hippocampal Cells.

in Biomolecules by Federico Fiorani, Martina Mandarano, Samuela Cataldi, Alessandra Mirarchi, Stefano Bruscoli, Francesco Ragonese, Bernard Fioretti, Toshihide Kobayashi, Nario Tomishige, Tommaso Beccari, Claudia Floridi, Cataldo Arcuri, Elisabetta Albi

TLDR

  • The study found that high doses of ceramide induce opposite cellular responses compared to low doses, with implications for sphingolipid metabolism and glioblastoma treatment.

Abstract

Ceramide is a critical molecule in both the physiology and pathology of the central nervous system. The most studied aspect is its effect on embryonic/stem cells. A salient question is whether low doses of ceramide induce neuronal differentiation without interfering with sphingolipid metabolism and whether high doses can be used in glioblastoma for their cytotoxic effect. Here, we examined the effect of a high dose of ceramide (13 µM) on HN9.10e cells. Interestingly, 13 µM ceramide induced an immediate increase in cell viability, followed by an increase in the number of mitochondria. Microscopic and morphometric analysis revealed a decrease in the number of differentiated cells with 13 µM compared to 0.1 µM but with longer neurites. Furthermore, the lipidomic study demonstrated an increase in the formation of medium-long-chain ceramide and sphingomyelin species and sphingosine 1 phosphate. Sphingolipid modification correlated with,, andgene expression coding for neutral sphingomyenase 2, ceramidase 2, and sphingosine kinase 2, respectively. Overall, our data show that the variety of responses to ceramide of the same cell type is dependent on the concentration used. Low doses do not affect sphingolipid metabolism, and high doses do so with a different cellular response.

Overview

  • The study aimed to investigate the effect of high dose ceramide (13 µM) on HN9.10e cells and its impact on sphingolipid metabolism.
  • The research examined whether high doses of ceramide can be used to induce cytotoxic effects on glioblastoma cells.
  • The study found that 13µM ceramide induced opposite cellular responses compared to 0.1µM ceramide, with implications for sphingolipid metabolism.

Comparative Analysis & Findings

  • Low doses of ceramide (0.1µM) did not affect sphingolipid metabolism, whereas high doses (13µM) did.
  • High doses of ceramide induced an immediate increase in cell viability, followed by an increase in mitochondrial number, and differentiation of cells.
  • Lipidomic analysis revealed increased formation of medium-long-chain ceramide and sphingomyelin species and sphingosine 1 phosphate in response to high doses of ceramide.

Implications and Future Directions

  • The study's findings have implications for understanding the role of ceramide in glioblastoma treatment and the development of new therapeutic strategies.
  • Future research could investigate the optimal concentrations of ceramide for its therapeutic effects on glioblastoma and its potential interactions with other molecules.
  • The study's results also suggest that ceramide may be a useful tool for understanding the regulation of sphingolipid metabolism in various cellular contexts.
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