October 1, 1996The FASEB Journal
Sphingolipid metabolism and cell growth regulation
Authors
Discussion
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Implication
Review demonstrates concentration-dependent control of cell growth and apoptosis by sphingolipid metabolites in cell lines, indicating their dual roles as second messengers and mediators of disease.
Key Points
- To review the metabolic pathways of sphingolipids and elucidate how their downstream metabolites act as second messengers to regulate cell proliferation, differentiation, and apoptosis.
- Synthesized molecular mechanisms involving agonist-induced sphingomyelin breakdown triggered by tumor necrosis factor-alpha, interleukin-1beta, nerve growth factor, and platelet-derived growth factor.
- Evaluated concentration-dependent responses to sphingosine and sphingosine 1-phosphate in Swiss 3T3 cell models.
- Analyzed the effects of ceramide synthase inhibition by fumonisin mycotoxins on endogenous sphingoid base accumulation and cell fate.
- Sphingosine and sphingosine 1-phosphate stimulate cell growth at low concentrations through intracellular calcium mobilization and activation of the MAP kinase pathway and AP-1 transcription factors.
- Elevated concentrations of sphingosine, ceramide, or related sphingoid bases induce cytotoxicity and programmed cell death (apoptosis) depending on cell type and intracellular localization.
- Blockade of ceramide synthase by fumonisins leads to abnormal accumulation of endogenous sphingoid bases, driving aberrant growth stimulation or toxicity.
Cite This Study
Spiegel et al. (1996) studied this question.