Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death

Author(s): Thomas D. Mullen, Lina M. Obeid.

Abstract:

Programmed cell death, or apoptosis, is a complex process whereby eukaryotic cells react to physiologic or pathophysiologic stimuli by undergoing genetically programmed suicide. Programmed cell death involves many well-characterized signaling pathways including permeabilization of the mitochondrial outer membrane and activation of caspases. Other pathways, such as pro-apoptotic lipid signaling, are less understood despite many years of study. The sphingolipid ceramide has received considerable attention as a key regulator of programmed cell death, yet the mechanisms of its up-regulation and ability to control cell fate remain ill-defined. In this review, we will examine the connections between sphingolipid metabolism and programmed cell death with a focus on the role of de novo sphingolipid synthesis and sphingosine salvage in producing pro-apoptotic ceramide. We will also highlight the evidence supporting an increasingly complex role for ceramide in regulating apoptosis and provide a framework in which to ask new questions about the functions of this enigmatic lipid.

Keywords: Ceramide synthase, Ceramide, Apoptosis, De novo sphingolipid synthesis, Programmed cell death, Salvage pathway, Serine palmitoyl transferase, Sphingomyelinase, (karyorrhexis, autophagosomes

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Article Details

VOLUME: 12
ISSUE: 4
Year: 2012
Page: [340 - 363]
Pages: 24
DOI: 10.2174/187152012800228661
Price: $58