Inhibition of Sphingomyelin Hydrolysis: Targeting the Lipid Mediator Ceramide as a Key Regulator of Cellular Fate

$63.10 plus tax (Refund Policy)

Buy Article:

Abstract:

Ceramide, an intracellular lipid mediator, is generated by transient hydrolysis of sphingomyelin in response to agonists inducing inflammation and apoptosis, ionizing radiation, chemotherapeutics or ischaemia/reperfusion. An elevated intracellular ceramide production is predominantly induced by an elevated hydrolytic activity of sphingomyelinases or by the activity of enzymes controlling de novo synthesis, such as ceramide synthase. Ceramide is implicated in various cellular responses, acting as an autonomous intracellular effector in cell cycle regulation, differentiation, senescence, and apoptosis. Furthermore, by changing membrane properties it contributes to the assembly and interactions of various signal transduction molecules. The lipid mediator is subsequently metabolised by ceramidase and sphingosine kinase, and other key players, which determine the dynamic balance between the intracellular levels of ceramide and its breakdown products (the ceramide/S1P rheostat). Together with sphingomyelinases, they are crucial for cell signalling, cellular survival or initiation of apoptosis. Sphingomyelinases are regarded as key enzymes in the regulated activation of the sphingomyelin cycle. Up to now, five isoforms of sphingomyelinases are known, differentiated by agonists, intracellular localization, pH optimum and essential co-factors. Herein, we focus on the biochemical background and the action of pharmacologically interesting compounds capable of interfering with sphingomyelinases and outline their potential implications for medicinal chemistry.

Keywords: Sphingomyelinase; apoptosis; inflammation; rafts

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709788682182

Affiliations: Department for Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany.

Publication date: June 1, 2009

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more