Altered de novo sphingolipid biosynthesis is involved in the serum deprivation-induced cell death in LLC-PK1 cells.
Fumonisin B1, a specific inhibitor of ceramide synthase, and ISPI (Myriocin), a serine palmitoyltransferase 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.
Yu
Min U
MU
College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Yoo
Jae Myung
JM
Lee
Youn Sun
YS
Lee
Yong Moon
YM
Hong
Jin Tae
JT
Oh
Ki Wan
KW
Song
Sukgil
S
Yun
Yeo Pyo
YP
Yoo
Hwan Soo
HS
Oh
Seikwan
S
D000818:Animals; D016923:Cell Death; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D037341:Fumonisins / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology*; D044967:Serum; D013107:Sphingolipids / Q000096:biosynthesis*; D013552:Swine
D003470:Culture Media; D004791:Enzyme Inhibitors; D037341:Fumonisins; D013107:Sphingolipids; C056933:fumonisin B1