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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Nitric oxide and sphingolipids: mechanisms of interaction and role in cellular pathophysiology

Cristiana Perrotta1 / Clara De Palma2 / Emilio Clementi3

1Stem Cell Research Institute, San Raffaele Scientific Institute, I-20132 Milano, Italy

2Stem Cell Research Institute, San Raffaele Scientific Institute, I-20132 Milano, Italy

3E. Medea Scientific Institute, I-23842 Bosisio Parini, and Department of Preclinical Sciences, University of Milano, I-20157 Milano, Italy

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 11, Pages 1391–1397, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2008.155, September 2008

Publication History

Received:
2008-06-27
Accepted:
2008-07-22
Published Online:
2008-09-11

Abstract

Nitric oxide is a short-lived messenger with pleiotropic roles in the regulation of cell patho-physiological processes, including survival, death, proliferation and differentiation. Increasing evidence over the last few years has shown that nitric oxide effects in apoptosis, growth and differentiation originate in significant part from its interplay with signalling members of the sphingolipid family. In many cell types belonging to different lineages, nitric oxide and sphingolipids interact in two-way pathways leading to regulation of the activity and expression of enzymes involved in each other's signalling events. These crosstalk signalling events involve various sphingolipids, with key roles for ceramide and sphingosine-1-phosphate, and signal transduction molecules downstream of nitric oxide, with cyclic GMP as a main player. The biological implications of some of these interactions are now being understood. The best-characterised so far, the mutual regulation of sphingomyelinases and endothelial nitric oxide synthase, acts as a tuning system in crucial patho-physiological processes such as inflammation, proliferation and cell death.

Keywords: apoptosis; ceramide; cyclic GMP; inflammation; nitric oxide; sphingomyelinases; sphingosine-1-phosphate

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