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Multifaceted roles of sphingosine-1-phosphate: how does this bioactive sphingolipid fit with acute neurological injury?
J Neurosci Res 2008; 86(7):1419-33JN

Abstract

Sphingosine-1-phosphate (Sph-1-P) is an essential bioactive sphingolipid metabolite that has currently become the focus of intense interest. Sph-1-P is generated by the enzyme sphingosine kinase (SphK) in response to diverse stimuli, including growth factors, cytokines, and G-protein-coupled receptor (GPCR) agonists. Its precursor, sphingosine (Sph), is produced from the precursor ceramide (Cer) via a ceramidase (CDase) that is released from membrane sphingomyelin (SPM) by sphingomyelinases (SMase). Accumulating evidence indicates that Sph-1-P is the key regulatory lipid involved in the metabolism of sphingolipids and is involved in the control of numerous aspects of cell physiology, including mitogenesis, differentiation, migration, and apoptosis. These actions of Sph-1-P are mediated by a family of high-affinity S1P receptors, named S1P1-5, which are coupled differentially via G(i), G(q), G(12/13), and Rho to multiple effector systems, including adenylate cyclase, phospholipases C (PLC) and D (PLD), extracellular-signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nonreceptor tyrosine kinases. In this Review, we accumulate available evidence implying that sphingolipid signaling may represent a novel neuroprotective target to counteract the pathophysiology of acute brain and spinal cord injury in regard to apoptotic cell death mechanisms, mitochondrial dysfunction, lipid hydrolysis, and oxidative damage mechanisms. Furthermore, we discuss how Sph-1-P agonist approaches might be expected to increase the resistance of the central nervous system to injury by promoting neurotrophic activity, neurogenesis, and angiogenesis. On the other hand, antagonists of certain Sph-1-P-related activity might possess proregenerative effects via promotion of neurite growth and inhibition of astrogliotic scarring.

Authors+Show Affiliations

Spinal Cord and Brain Injury Research Center (SCoBIRC) and Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0509, USA. ising2@uky.eduNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18058948

Citation

Singh, Indrapal N., and Edward D. Hall. "Multifaceted Roles of Sphingosine-1-phosphate: How Does This Bioactive Sphingolipid Fit With Acute Neurological Injury?" Journal of Neuroscience Research, vol. 86, no. 7, 2008, pp. 1419-33.
Singh IN, Hall ED. Multifaceted roles of sphingosine-1-phosphate: how does this bioactive sphingolipid fit with acute neurological injury? J Neurosci Res. 2008;86(7):1419-33.
Singh, I. N., & Hall, E. D. (2008). Multifaceted roles of sphingosine-1-phosphate: how does this bioactive sphingolipid fit with acute neurological injury? Journal of Neuroscience Research, 86(7), pp. 1419-33.
Singh IN, Hall ED. Multifaceted Roles of Sphingosine-1-phosphate: How Does This Bioactive Sphingolipid Fit With Acute Neurological Injury. J Neurosci Res. 2008 May 15;86(7):1419-33. PubMed PMID: 18058948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multifaceted roles of sphingosine-1-phosphate: how does this bioactive sphingolipid fit with acute neurological injury? AU - Singh,Indrapal N, AU - Hall,Edward D, PY - 2007/12/7/pubmed PY - 2008/7/9/medline PY - 2007/12/7/entrez SP - 1419 EP - 33 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 86 IS - 7 N2 - Sphingosine-1-phosphate (Sph-1-P) is an essential bioactive sphingolipid metabolite that has currently become the focus of intense interest. Sph-1-P is generated by the enzyme sphingosine kinase (SphK) in response to diverse stimuli, including growth factors, cytokines, and G-protein-coupled receptor (GPCR) agonists. Its precursor, sphingosine (Sph), is produced from the precursor ceramide (Cer) via a ceramidase (CDase) that is released from membrane sphingomyelin (SPM) by sphingomyelinases (SMase). Accumulating evidence indicates that Sph-1-P is the key regulatory lipid involved in the metabolism of sphingolipids and is involved in the control of numerous aspects of cell physiology, including mitogenesis, differentiation, migration, and apoptosis. These actions of Sph-1-P are mediated by a family of high-affinity S1P receptors, named S1P1-5, which are coupled differentially via G(i), G(q), G(12/13), and Rho to multiple effector systems, including adenylate cyclase, phospholipases C (PLC) and D (PLD), extracellular-signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nonreceptor tyrosine kinases. In this Review, we accumulate available evidence implying that sphingolipid signaling may represent a novel neuroprotective target to counteract the pathophysiology of acute brain and spinal cord injury in regard to apoptotic cell death mechanisms, mitochondrial dysfunction, lipid hydrolysis, and oxidative damage mechanisms. Furthermore, we discuss how Sph-1-P agonist approaches might be expected to increase the resistance of the central nervous system to injury by promoting neurotrophic activity, neurogenesis, and angiogenesis. On the other hand, antagonists of certain Sph-1-P-related activity might possess proregenerative effects via promotion of neurite growth and inhibition of astrogliotic scarring. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/18058948/Multifaceted_roles_of_sphingosine_1_phosphate:_how_does_this_bioactive_sphingolipid_fit_with_acute_neurological_injury L2 - https://doi.org/10.1002/jnr.21586 DB - PRIME DP - Unbound Medicine ER -