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Journal of Lipids
Volume 2018, Article ID 3646725, 11 pages
https://doi.org/10.1155/2018/3646725
Review Article

Ceramide and Ischemia/Reperfusion Injury

Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA

Correspondence should be addressed to Edward H. Schuchman; ude.mssm@namhcuhcs.drawde

Received 2 October 2017; Accepted 21 December 2017; Published 21 January 2018

Academic Editor: Afaf El-Ansary

Copyright © 2018 Xingxuan He and Edward H. Schuchman. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ceramide, a bioactive membrane sphingolipid, functions as an important second messenger in apoptosis and cell signaling. In response to stresses, it may be generated by de novo synthesis, sphingomyelin hydrolysis, and/or recycling of complex sphingolipids. It is cleared from cells through the activity of ceramidases, phosphorylation to ceramide-1-phosphate, or resynthesis into more complex sphingolipids. Ischemia/reperfusion (IR) injury occurs when oxygen/nutrition is rapidly reintroduced into ischemic tissue, resulting in cell death and tissue damage, and is a major concern in diverse clinical settings, including organ resection and transplantation. Numerous reports show that ceramide levels are markedly elevated during IR. Mitochondria are major sites of reactive oxygen species (ROS) production and play a key role in IR-induced and ceramide-mediated cell death and tissue damage. During the development of IR injury, the initial response of ROS and TNF-alpha production activates two major ceramide generating pathways (sphingomyelin hydrolysis and de novo ceramide synthesis). The increased ceramide has broad effects depending on the IR phases, including both pro- and antiapoptotic effects. Therefore, strategies that reduce the levels of ceramide, for example, by modulation of ceramidase and/or sphingomyelinases activities, may represent novel and promising therapeutic approaches to prevent or treat IR injury in diverse clinical settings.