Planta Med 2012; 78(5): 434-439
DOI: 10.1055/s-0031-1298155
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Terpene Alcohols Inhibit De Novo Sphingolipid Biosynthesis

Kyong-Oh Shin1 , Myong-Yong Park1 , Cho-Hee Seo1 , Yong-Ill Lee2 , Hyun Sik Kim3 , Hwan-Soo Yoo1 , Jin Tae Hong1 , Jae-Kyung Jung1 , Yong-Moon Lee1
  • 1College of Pharmacy and MRC, Chungbuk National University, Chongju, Korea
  • 2Department of Chemistry, Changwon National University, Changwon, Korea
  • 3Division of Mass Spectrometry Research, Korea Basic Science Institute, Ochang, Korea
Further Information

Publication History

received October 13, 2011 revised Dec. 14, 2011

accepted Dec. 15, 2011

Publication Date:
24 January 2012 (online)

Abstract

The terpene alcohols geranyllinalool, phytol (diterpene alcohol), and farnesol (sesquiterpene alcohol) were newly found to inhibit sphingolipid de novo biosynthesis in LLC-PK1 cells (pig kidney epithelial cells). A simple chromatographic bioassay was established for the screening of inhibitory compounds able to reduce the amount of sphinganine, an intermediate metabolite of sphingolipid biosynthesis. The screening strategy was based on the degree of suppression of fumonisin B1 (FB1)-induced sphinganine accumulation following co-treatment with selected terpene alcohols. L-cycloserine and ISP-1, specific serine palmitoyltransferase (SPT) inhibitors, were used as positive controls. Our results show that measuring reduced sphinganine levels after treatment with 2 µM FB1 in combination with the putative inhibitory compounds provides a useful screening bioassay for evaluating compounds causing sphingolipid depletion. Intracellular sphinganine concentrations were analyzed using the fluorescent peak areas of the o-phthalaldehyde (OPA) derivatives of sphinganine eluted with 87 % acetonitrile on a reversed-phase column. Geranyllinalool, phytol, and farnesol were identified as novel SPT inhibitors that reduce FB1-induced sphinganine accumulation and thus inhibit the first step of sphingolipid de novo synthesis.

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Prof. Yong-Moon Lee

College of Pharmacy and MRC
Chungbuk National University

San 48, Kaesin-Dong, Hungduk-Ku

Chongju 361-763

Korea

Phone: +82 4 32 61 28 25

Fax: +82 4 32 68 27 32

Email: ymleefn@cbnu.ac.kr