Regulation of sphingomyelin metabolism

doi:10.1016/j.pharep.2015.12.008

Pharmacological Reports

Volume 68, Issue 3, June 2016, Pages 570-581

https://doi.org/10.1016/j.pharep.2015.12.008 Get rights and content

Abstract

Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD).

Section snippets

SM – structure and function

SM is the most abundant eukaryotic sphingolipid (SF) which constitutes one of the major components of the plasma membrane (PM). The structural function of SM in a cell is determined by chemical structure of a phospholipid. Specifically, the hydrophilic head and the hydrophobic tail of the phospholipid molecules enable them to form a double layer structure, known as a lipid bilayer. SM (N-acyl-sphingosine-1-phosphorylcholine) is composed of ceramide which comprises a sphingoid backbone, an

Ischemia/reperfusion

Cerebral ischemia is a condition of decreased tissue perfusion resulting in an inadequate supply of oxygen, glucose and other metabolites, and the subsequent reperfusion triggering multiple signaling cascades, which leads to brain injury. Various factors/pathways have been described in the literature as crucial for ischemia-induced neurodegeneration. Numerous changes, among others, have been observed in SM metabolism, frequently noted as essential for neuronal death or survival in

Summary

SM is the most abundant eukaryotic SF component of the plasma membrane. SM with different fatty acid chains has the ability to create unique compositions of lipid rafts thereby it can strongly modify the property of the PM. The SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways which create a balance between SM synthesis (SMSs) and degradation (SMases). Physiological roles of SMSs and SMases is not sufficiently recognized. The activities of these enzyme undergo

Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.

Funding

The authors declare that funding source(s) had no involvement in preparing this manuscript.

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Review articleRegulation of sphingomyelin metabolism

Abstract

Section snippets

SM – structure and function

Ischemia/reperfusion

Summary

Conflict of interest

Funding

Biophys J

J Biol Chem

FEBS Lett

Biophys J

Biophys J

J Biol Chem

J Biol Chem

Biochim Biophys Acta

Biophys J

Biochim Biophys Acta

Biophys J

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Biochim Biophys Acta

J Biol Chem

FEBS Lett

J Lipid Res

Biochim Biophys Acta

Biochim Biophys Acta

J Biol Chem

J Biol Chem

Biochim Biophys Acta

J Biol Chem

J Biol Chem

J Biol Chem

Blood

Prog Lipid Res

Int J Biochem Cell Biol

Biochem Biophys Res Commun

J Lipid Res

Biochem Biophys Res Commun

Biochem Pharmacol

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Thromb Res

Arch Biochem Biophys

J Biol Chem

Neurochem Int

Cell Signal

FEBS Lett

Am J Pathol

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Review article
Regulation of sphingomyelin metabolism