Page Banner

United States Department of Agriculture

Agricultural Research Service

Title: Inhibition of DE Novo Sphingolipid Biosynthesis Reduces Expression of P42 Map Kinase (Erk2) in Llc-Pk1 Cells

Authors
item Rentz, Sarah - PHARM BIOMED SCI/UGA
item Showker, Adele
item Meredith, Filmore
item Riley, Ronald

Submitted to: Mycopathologia
Publication Type: Abstract Only
Publication Acceptance Date: January 15, 2002
Publication Date: June 1, 2002
Citation: RENTZ, S.S., SHOWKER, A.J., MEREDITH, F.I., RILEY, R.T. 2002. INHIBITION OF DE NOVO SPHINGOLIPID BIOSYNTHESIS REDUCES EXPRESSION OF P42 MAP KINASE (ERK2) IN LLC-PK1 CELLS. MYCOPATHOLOGIA. v.155. Abstract p.39.

Interpretive Summary: Abstract only

Technical Abstract: Fumonisin B1 (FB1) is a fungal toxin produced by Fusarium verticillioides, a common pathogen of corn. FB1 inhibits ceramide synthase, a key enzyme in the de novo sphingolipid biosynthesis and turnover pathways. Free sphingoid bases, sphingoid base metabolites, ceramide and more complex sphingolipids generated in the biosynthesis and turnover pathways modulate many downstream signals including mitogen-activated protein (MAP) kinases. In LLC-PK1 (porcine renal proximal tubule epithelial) cells, FB1 inhibits cell proliferation, induces apoptosis, and alters cell-cell contact in a time and concentration-dependent manner. The increased apoptosis and decreased cell proliferation can be prevented by ISP-1, an inhibitor of serine palmitoyltransferase, the first and rate-limiting enzyme in de novo sphingolipid biosynthesis. However, the downstream signaling pathways that are affected by FB1 disruption of sphingolipid metabolism are not well understood. The purpose of this study was to determine in LLC-PK1 cells changes in expression of p42 MAP kinase, also called extracellular signal-regulated kinase 2 (ERK2) in response to a FB1 concentration known to inhibit cell growth and induce increased apoptosis. Significant inhibition of cell growth was first noted after 48 h exposure to FB1 (50 µM). However, p42 MAP kinase was decreased at 24 h and at all subsequent time-points (48 and 72 h) relative to the concurrent control. FB1 treatment in the absence of serum further reduced the expression of p42 at 48 and 72 h. In order to determine if decreased p42 expression was due to FB1-induced elevation in free sphingoid bases, cells were treated with a combination of ISP-1 and FB1. ISP-1 did not reverse the decreased expression of p42 caused by FB1. However, ISP-1 alone also caused a decreased expression of p42, indicating that FB1-mediated changes in expression of p42 could be independent of alterations in sphingoid bases but dependent on de novo sphingolipid biosynthesis.

Last Modified: 10/21/2014
Footer Content Back to Top of Page