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
Anti-Cancer Agents in Medicinal Chemistry
Title:Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death
Volume: 12 Issue: 4
Author(s): Thomas D. Mullen and Lina M. Obeid
Affiliation:
Keywords: Ceramide synthase, Ceramide, Apoptosis, De novo sphingolipid synthesis, Programmed cell death, Salvage pathway, Serine palmitoyl transferase, Sphingomyelinase, (karyorrhexis, autophagosomes
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.
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Cite this article as:
Mullen Thomas D. and Obeid Lina M., Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death , Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (4) . https://dx.doi.org/10.2174/187152012800228661
DOI https://dx.doi.org/10.2174/187152012800228661 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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