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KMID : 0043320010240020136
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Archives of Pharmacal Research
2001 Volume.24 No. 2 p.136 ~ p.143
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Differential Effects of Fumonisim B1 on Cell Death in Cultured Cells: the Significance of the Elevated Sphinganine
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Yu CH
Lee YM/Yun YP/Yoo HS
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Abstract
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Fumonisms are specific inhibitors of ceramide synthase in sphingolipid metabolism. An alteration in sphingolipid metabolism as a results of fumonism exposure is related to cell death(Yoo et al.,1992). The objective of this study was to investigate whether elevated free sphinganine levels are related to the sensitivity of cultured cells fumonism exposure. Fumonisn B1 elevated the intracellular free sphinganine concentraions in both LLC-PK1 and Chinese hamster ovary(CHO)cells. However, CHO cells are resistant to fumonisin cytotoxicity at 50mcM, while LLC-PK1 cells are sensitive at concentrations greaer than 35mcM. The intracellular concentration of free sphinganine in LLG-PK1 cells treated at 50mcM fumonisin B1 for 72h was approximately 1450pmol/mg protein relative to the 37pmol observed in the control culture. Under the same conditions, the population of apoptotic cells in the 50mcM fumonisin B1-treated culture was aproximately 37% of the total compared to 12% in the control. The caspae III-like actitvity after 72h in the 50mcM fumonisin B1-exposed culture increased to conditions to approximaterly 50pmol/mg protein/hr compared to 6pmol/mg, protein/hr in the control. L-cycloserine, a serine palmitoyltransferase inhibitor, reduced the fumonisin B1 caspase III-like activity down to the control level. Under the same culture condition the intracellular concentration of free sphinganine after L-chcloserine plus fumonisin B1 treatment was 140pmol/mg protein compared to 1450pmol/mg protein in fumonisin B1 alone. The intracellular concentration of free sphinganine in CHO cells treated with 50mcM fumonisin B1 for 72h was approximaaterly 460pmol/mg protein, indicating that the mass amount of elevated free sphinganine in the CHO cells was about 32% of that in LLC-PK1 cells. Adding exogenous sphinganine to the CHO cells along with 50mcM fumonisin B1 treatment for 72h caused both necrosis and apoptosis. In conclusin, the elevated endogenous sphinganine acts as a contribution factor to the fumonisin-induced cell death.
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