Affordable Access

deepdyve-link
Publisher Website

Role of bioactive sphingolipids in physiology and pathology.

Authors
  • Gomez-Larrauri, Ana1, 2
  • Presa, Natalia1
  • Dominguez-Herrera, Asier1
  • Ouro, Alberto1
  • Trueba, Miguel1
  • Gomez-Muñoz, Antonio1
  • 1 Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao 48080, Bizkaia, Spain. , (Spain)
  • 2 Respiratory Department, Cruces University Hospital, Barakaldo 48903, Bizkaia, Spain. , (Spain)
Type
Published Article
Journal
Essays in biochemistry
Publication Date
Sep 23, 2020
Volume
64
Issue
3
Pages
579–589
Identifiers
DOI: 10.1042/EBC20190091
PMID: 32579188
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Sphingolipids are a class of complex lipids containing a backbone of sphingoid bases, namely the organic aliphatic amino alcohol sphingosine (Sph), that are essential constituents of eukaryotic cells. They were first described as major components of cell membrane architecture, but it is now well established that some sphingolipids are bioactive and can regulate key biological functions. These include cell growth and survival, cell differentiation, angiogenesis, autophagy, cell migration, or organogenesis. Furthermore, some bioactive sphingolipids are implicated in pathological processes including inflammation-associated illnesses such as atherosclerosis, rheumatoid arthritis, inflammatory bowel disease (namely Crohn's disease and ulcerative colitis), type II diabetes, obesity, and cancer. A major sphingolipid metabolite is ceramide, which is the core of sphingolipid metabolism and can act as second messenger, especially when it is produced at the plasma membrane of cells. Ceramides promote cell cycle arrest and apoptosis. However, ceramide 1-phosphate (C1P), the product of ceramide kinase (CerK), and Sph 1-phosphate (S1P), which is generated by the action of Sph kinases (SphK), stimulate cell proliferation and inhibit apoptosis. Recently, C1P has been implicated in the spontaneous migration of cells from some types of cancer, and can enhance cell migration/invasion of malignant cells through interaction with a Gi protein-coupled receptor. In addition, CerK and SphK are implicated in inflammatory responses, some of which are associated with cancer progression and metastasis. Hence, targeting these sphingolipid kinases to inhibit C1P or S1P production, or blockade of their receptors might contribute to the development of novel therapeutic strategies to reduce metabolic alterations and disease. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Report this publication

Statistics

Seen <100 times