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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor metastasis ...read more
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...read more
Metalloenzymes and Cancer: Μetalloenzyme Ιnhibitors and Artificial Metalloenzymes as anti-cancer agents
Metalloenzymes are enzymes containing metal ions, which are directly bound to the enzyme and play a role in promoting catalysis. About one-third of all enzymes known so far are metalloenzymes [1]. Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
miR-629-3p Level Significantly Predicts Prognosis in Glioblastoma Patients Treated with Temozolomide Chemotherapy
Current Signal Transduction Therapy Mechano-Regulation of Alternative Splicing
Current Genomics Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)
Recent Patents on Anti-Cancer Drug Discovery Mucoadhesive Chitosan Derivatives as Novel Drug Carriers
Current Pharmaceutical Design Isolation, Structural Determination, and Evaluation of the Biological Activity of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol [20(S)-25-OCH3-PPD], a Novel Natural Product from Panax notoginseng
Medicinal Chemistry Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes
Current Neuropharmacology Regulation of Innate Immune Responses in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Gold Nanoparticle-Based Drug Delivery Platform for Antineoplastic Chemotherapy
Current Drug Metabolism Anticancer Mechanisms of Bioactive Peptides
Protein & Peptide Letters α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease
Current Alzheimer Research The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Current Cancer Drug Targets Herpesvirus Saimiri-Based Gene Delivery Vectors
Current Gene Therapy Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas
Current Stem Cell Research & Therapy Antineovascular Agents in the Treatment of Eye Diseases
Current Pharmaceutical Design Modulation of the Endocannabinoid System by Lipid Rafts
Current Medicinal Chemistry Glimpse into the Cellular Internalization and Intracellular Trafficking of Lipid- Based Nanoparticles in Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry The Role of Integrins in Glioma Biology and Anti-Glioma Therapies
Current Pharmaceutical Design Targeting Ion Channels for the Treatment of Glioma
Mini-Reviews in Medicinal Chemistry Salmonella as Live Trojan Horse for Vaccine Development and Cancer Gene Therapy
Current Gene Therapy Targeting Aberrant TGF-β Signaling in Pre-Clinical Models of Cancer
Anti-Cancer Agents in Medicinal Chemistry