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Disruption of Sphingolipid Metabolism as a Potential Mechanism of Fumonisin Inhibition of Cell Growth in $LLC-PK_1$ Cells
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  • Disruption of Sphingolipid Metabolism as a Potential Mechanism of Fumonisin Inhibition of Cell Growth in $LLC-PK_1$ Cells
  • Disruption of Sphingolipid Metabolism as a Potential Mechanism of Fumonisin Inhibition of Cell Growth in $LLC-PK_1$ Cells
저자명
Yoo. Hwan-Soo,Yun. Yeo-Pyo
간행물명
한국독성학회지
권/호정보
1995년|11권 1호|pp.1-8 (8 pages)
발행정보
한국독성학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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Fumonisins are a family of mycotoxins produced by the fungus Fusarium moniliforme which is a common contaminant in corn. Fumonisins are potent inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase), key enzymes in sphingolipid metabolism. The purpose of this study was to provide the evidence that the elevated levels of free sphingoid bases (primarily sphinganine) and depletion of complex sphingolipids were closely related to the inhibition of cell growth in LLC-$PK_1$ cells exposed to fumonisin $B_1$$(leq 35 {mu}M)$. Concentrations of fumonisin $B_1$ between 10 and $35 {mu}M$ were known to inhibit cell growth without cytotoxicity in $LLC-PK_1$ cells (Yoo et al. Toxicol. Appl. Pharmacol. 114, 9-15, 1992). Cells exposed to 35$mu M$ fumonisin B$_1$ for 48 and 72 hr developed a fibroblast-like (elongated and spindle-shaped) appearance and were less confluent than normal cells. At between 24 and 48 hr after exposure to fumonisin $B_1$ cells were beginning to show the inhibition of cell growth and at 72 hr the number of viable cells in fumonisin-treated cultures was about 50% of concurrent control cultures. During the 24 hr lag period preceding inhibition of cell growth, the free sphinganine levels in cells exposed to $35 {mu}M$ fumonisin $B_1$ were highly elevated (approximately 230 fold higher than normal cells). The elevated levels of free sphinganine were $435pm14$$pmoles/{10^6}$ cells at 48 hr and approximately TEX>$333pm11$</TEX>$pmoles/{10^6}$ cells in cells exposed to $35{mu}M$ fumonisin$B_1$ at 72 hr, while the levels of free sphinganine in normal cells were less than 2$pmoles/{10^6}$ cells. Under the same condition, depletion of intracellular complex sphingolipids as a consequence of fumonisin inhibition of de novo sphingolipid biosynthesis and turnover pathway was appeared. Content of free sphingold bases in dividing cells was more elevated than in confluent cells at 24-48 hr after cells were exposed to $20{mu}M$ fumonisin $B_1$. The dividing cells were showing the inhibition of cell growth at 48-72 hr and $20{mu}M$ fumonisin $B_1$. The results of this study support the hypothesis that the inhibition of cell growth is very well related to the disruption of sphingolipid metabolism in $LLC-PK_1$ cells.