Altered de novo sphingolipid biosynthesis is involved in the serum deprivation-induced cell death in LLC-PK1 cells

Min U. Yu, Myung Yoo Jae, Sun Lee Youn, Moon Lee Yong, Tae Hong Jin, Wan Oh Ki, Sukgil Song, Pyo Yun Yeo, Soo Yoo Hwan, Seikwan Oh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 languageEnglish
Pages (from-to)2085-2094
Number of pages10
JournalJournal of Toxicology and Environmental Health - Part A
Volume67
Issue number23-24
DOIs
StatePublished - 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: yoohs@chungbuk.ac.kr

Fingerprint

Dive into the research topics of 'Altered de novo sphingolipid biosynthesis is involved in the serum deprivation-induced cell death in LLC-PK1 cells'. Together they form a unique fingerprint.

Cite this