Apoptosis and Sphingomyelin Hydrolysis

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Apoptosis and Sphingomyelin Hydrolysis

Apoptosis, a form of cell death that is coordinated by a set of defined biochemical pathways, exists throughout the animal kingdom. Its critically important roles in development, homeostasis, and disease have made this a topic of intensive research and sometimes even more intensive controversy. One of these areas of controversy concerns the role of ceramide, produced by the hydrolysis of sphing...

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Stress-induced apoptosis and the sphingomyelin pathway.

The sphingomyelin pathway is a ubiquitous, evolutionarily conserved signaling system initiated by hydrolysis of the plasma membrane phospholipid sphingomyelin to generate the second messenger ceramide. Sphingomyelin degradation is catalyzed by acid and neutral sphingomyelinase (SMase) isoforms. Most, if not all mammalian cells, appear capable of signaling though the sphingomyelin pathway. Diver...

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Enzymic hydrolysis of sphingomyelin in the presence of bile salts.

Sphingomyelin in mixed dispersion with bile salts was hydrolysed by the solubilized sphingomyelinase of rat brain lysosomes. In parallel studies, physical properties of these dispersions were determined. The kinetic curves that described the rate of hydrolysis as a function of increasing concentrations of bile salt were multiphasic. A region of very low activity was followed by an ascending por...

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Sphingomyelin Hydrolysis to Ceramide during the Execution Phase of Apoptosis Results from Phospholipid Scrambling and Alters Cell-Surface Morphology

Apoptosis is generally accompanied by a late phase of ceramide (Cer) production, the significance of which is unknown. This study describes a previously unrecognized link between Cer accumulation and phosphatidylserine (PS) exposure at the cell surface, a characteristic of the execution phase of apoptosis resulting from a loss of plasma membrane phospholipid asymmetry. Using a fluorescent sphin...

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A lipid analogue that inhibits sphingomyelin hydrolysis and synthesis, increases ceramide, and leads to cell death.

We report the synthesis and characterization of a novel thiourea derivative of sphingomyelin (AD2765). In vitro assays using pure enzyme and/or cell extracts revealed that this compound inhibited the hydrolysis of BODIPY-conjugated or 14C-labeled sphingomyelin by acid sphingomyelinase and Mg2+-dependent neutral sphingomyelinase. Studies in normal human skin fibroblasts further revealed that AD2...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2000

ISSN: 0021-9525,1540-8140

DOI: 10.1083/jcb.150.1.f5