doi: 10.1161/01.RES.0000241060.26659.d3
© 2006 American Heart Association, Inc.
Editorials |
Toward Solving the Riddle
The Enigma Becomes Less Mysterious
From the Cardiology Section, Veterans Affairs Medical Center, San Francisco, and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco.
Correspondence to Joel S. Karliner, MD, VA Medical Center (111C5), 4150 Clement St, San Francisco, CA 94121. E-mail joel.karliner@med.va.gov
See related article, pages 468–476
Key Words: sphingosine kinase-1 • sphingosine 1-phosphate • cardioprotection • enzyme regulation • four and a half LIM domain 2 (FLH2)
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
"It is a riddle wrapped in a mystery inside an enigma."1
The mythical Greek Sphinx posed riddles to passers-by. Those who could not answer met their demise until Oedipus solved the riddle and the Sphinx self-destructed. Ultimately the terms sphinx and enigma became associated and in 1884 J.L.W. Thudichum, known as the "Father of Neurochemistry," named the chemical backbone of sphingolipids for their enigmatic "Sphinx-like" properties. Recently, studies of sphingolipid actions have achieved increasing importance in understanding the pathophysiology of acute ischemia/reperfusion injury through studies of sphingosine kinase (SphK) and its end-product, sphingosine 1-phosphate (S1P). Activation of SphK is the final and rate-limiting enzymatic step in the synthesis of S1P, which is an intracellular and extracellular signaling molecule that regulates many important cellular processes including growth, survival, differentiation, cytoskeletal rearrangements, motility, angiogenesis, and calcium mobilization. In contrast, the sphingosine precursor ceramide is a growth-inhibiting lipid implicated in differentiation and apoptosis. These findings have led to the so-called "sphingolipid rheostat" hypothesis, which proposes that the relative levels of these lipids are important determinants of cell fate.2
It is now accepted that many of the actions of S1P are mediated by a family of G protein–coupled S1P receptor isoforms, termed S1P1–5. With regard to the cardiovascular system, platelets store and release S1P, which is known to regulate endothelial function and signaling. There is a substantial gradient between intracellular and extracellular concentrations of S1P. In human serum estimates of S1P concentration range from 0.5 to 1 µmol/L or more, whereas
Related Article:
Circ. Res. 2006 99: 468-476.
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