Abstract
Fumonisin B1, a specific inhibitor of ceramide synthase, and ISP1 (Myriocin), a serine palmitoyl-transferase inhibitor, modulate the de novo sphingolipid biosynthesis pathway. This study was conducted to determine whether serum deprivation-induced cell death is regulated by de novo sphingolipid biosynthesis in pig kidney LLC-PK1 cells. Serum withdrawal from the culture medium produced cell death in LLC-PK1 cells. Fumonisin B1 at concentrations ranging from 5 M to 30 M delayed until 48 h this cell death resulting from the absence of fetal bovine serum (FBS) in cell culture. Pretreatment of cultured cells with fumonisin B1 in the presence of serum for 24 h increased by approximately 70% this cytoprotective activity of fumonisin B1 against serum deprivation-induced cell death. Serum deprivation increased sphingolipid biosynthesis threefold compared to 5% serum-enriched culture. Fumonisin B1 at 5-30 M lowered the content of total complex sphingolipids to levels of 50% and 77% of the content in serum-enriched culture, although the concentration of intracellular free sphinganine was elevated. ISP1 alone at greater than 1 nM concentration reduced total complex sphingolipid content to values in LLC-PK1 cells grown in the presence of 5% FBS. The results suggest that the de novo complex sphingolipid biosynthesis modulated by either fumonisin B1 or ISP1 may regulate serum deprivation-induced cell death in LLC-PK1 cells.
Original language | English |
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Pages (from-to) | 2085-2094 |
Number of pages | 10 |
Journal | Journal of Toxicology and Environmental Health - Part A |
Volume | 67 |
Issue number | 23-24 |
DOIs | |
State | Published - Dec 2004 |
Bibliographical note
Funding Information:This work was supported by a grant (R01-2002-000-00457-0) from the Basic Research Program of the Korea Science & Engineering Foundation and by Brain Korea 21 project in 2003. Address correspondence to Dr. Hwan Soo Yoo, College of Pharmacy, Chungbuk National University, 12 Gaesin-dong, Heungduk-ku, Cheongju, Chungbuk 361-763, Korea. E-mail: [email protected]