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Sphingolipids and cellular cholesterol homeostasis. Effect of ceramide on cholesterol trafficking and HMG CoA reductase activity.

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Title: Sphingolipids and cellular cholesterol homeostasis. Effect of ceramide on cholesterol trafficking and HMG CoA reductase activity.
Alternative Title: Ceramic and cholesterol homeostasis in cells
Author(s): Subbaiah, Papasani V.; Sowa, Jennifer M.; Singh, Dev K.
Subject(s): Sphingomyelin Ceramide ACAT HMG CoA reductase Sterol trafficking
Abstract: We previously showed that degradation of cellular sphingomyelin (SM) by SMase C results in a greater stimulation of cholesterol translocation to endoplasmic reticulum, compared to its degradation by SMase D. Here we investigated the hypothesis that the effect of SMase C is partly due to the generation of ceramide, rather than due to depletion of SM alone. Inhibition of hydroxymethylglutaryl CoA reductase (HMGCR) activity was used as a measure of cholesterol translocation. Treatment of fibroblasts with SMase C resulted in a 90% inhibition of HMGCR, whereas SMase D treatment inhibited it by 29%. Treatment with exogenous ceramides, or increasing the endogenous ceramide levels also inhibited HMGCR by 60-80%. Phosphorylation of HMGCR was stimulated by SMase C or exogenous ceramide. The effects of ceramide and SMase D were additive, indicating the independent effects of SM depletion and ceramide generation. These results show that ceramide regulates sterol trafficking independent of cellular SM levels.
Issue Date: 2008-06-01
Publisher: Elsevier
Citation Info: Subbaiah PV, Sowa JM, Singh DK. Sphingolipids and cellular cholesterol homeostasis. Effect of ceramide on cholesterol trafficking and HMG CoA reductase activity. Arch Biochem Biophys. 2008 Jun 1;474(1):32-8. Epub 2008 Mar 25. http://www.sciencedirect.com/science/journal/00039861
Description: http://info.sciencedirect.com/
URI: http://hdl.handle.net/10027/1151
ISSN: 1096-0384
Date Available in INDIGO: 2008-06-26
 

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