Activation of de novo synthetic pathway of ceramides is responsible for the initiation of hydrogen peroxide-induced apoptosis in HL-60 cells.

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Son JH, Yoo HH, Kim DH

Activation of de novo synthetic pathway of ceramides is responsible for the initiation of hydrogen peroxide-induced apoptosis in HL-60 cells.

J Toxicol Environ Health A. 2007 Aug;70(15-16):1310-8.

PubMed ID

17654249 [ View in PubMed

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Abstract

Sphingolipid metabolites in HL-60 cells were analyzed to gain an understanding of their roles in early events underlying hydrogen peroxide (H2O2)-induced apoptosis. Incubation of cells with H2O2 increased the intracellular levels of ceramides and sphinganine, but decreased those of ceramide 1-phosphates (ceramide 1-P) and sphingosine. The levels of sphingomyelins and sphingomyelinase (SMase) activities were not affected by H2O2 treatment. These results were similar to the profiles induced by daunorubicin, an activator of serine palmitoyl CoA transferase (SPT), suggesting that H2O2 stimulated the de novo synthetic pathway of ceramides. L-cycloserine and fumonisin B1 (FB1), specific inhibitors of de novo ceramide biosynthesis, suppressed the elevation of ceramides and sphinganine induced by H2O2, which consequently reduced apoptotic cell death. Collectively, these results demonstrated that H2O2 increased the intracellular concentrations of ceramides via activation of a de novo biosynthetic pathway, and the enhanced ceramides might initiate apoptosis in HL-60 cells.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Serine	Serine--pyruvate aminotransferase	Protein	Humans	Unknown	Not Available	Details