Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.

Abstract

Sphingolipids, first described in the brain in 1884, are important structural components of biological membranes of all eukaryotic cells. In recent years, several lines of evidence support the critical role of sphingolipids such as sphingosine, sphingosine-1-phosphate (S1P), and ceramide as anti- or pro-inflammatory bioactive lipid mediators in a variety of human pathologies including pulmonary and vascular disorders. Among the sphingolipids, S1P is a naturally occurring agonist that exhibits potent barrier enhancing property in the endothelium by signaling via G protein-coupled S1P1 receptor. S1P, S1P analogs, and other barrier enhancing agents such as HGF, oxidized phospholipids, and statins also utilize the S1P/S1P1 signaling pathway to generate membrane protrusions or lamellipodia, which have been implicated in resealing of endothelial gaps and maintenance of barrier integrity. A better understanding of sphingolipids mediated regulation of lamellipodia formation and barrier enhancement of the endothelium will be critical for the development of sphingolipid-based therapies to alleviate pulmonary disorders such as sepsis-, radiation-, and mechanical ventilation-induced acute lung injury.

• Authors: Panfeng Fu, Mark Shaaya, Anantha Harijith, Jeffrey R Jacobson, Andrei Karginov, Viswanathan Natarajan
• Journal: Current topics in membranes (Curr Top Membr) Vol. 82 Pg. 1-31 ( 2018) ISSN: 1063-5823 [Print] United States
• PMID: 30360778 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Lysophospholipids
• Reactive Oxygen Species
• Sphingolipids
• sphingosine 1-phosphate
• Simvastatin
• Phosphotransferases (Alcohol Group Acceptor)
• sphingosine kinase
• Sphingosine

Topics

• Acute Lung Injury (drug therapy)
• Endothelium, Vascular (drug effects, metabolism)
• Humans
• Lysophospholipids (metabolism)
• Phosphotransferases (Alcohol Group Acceptor) (metabolism)
• Pseudopodia (metabolism, pathology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Simvastatin (pharmacology, therapeutic use)
• Sphingolipids (metabolism)
• Sphingosine (analogs & derivatives, metabolism)