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Sphingolipids in inflammation: The s...

Pettus, Benjamin James.

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Sphingolipids in inflammation: The synergistic role of sphingosine-1-phosphate in COX-2 induction and ceramide-1-phosphate in cPLA(2) binding/translocation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Sphingolipids in inflammation: The synergistic role of sphingosine-1-phosphate in COX-2 induction and ceramide-1-phosphate in cPLA(2) binding/translocation./
Author:	Pettus, Benjamin James.
Description:	217 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0044.
Contained By:	Dissertation Abstracts International67-01B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3200389
ISBN:	9780542495946

Sphingolipids in inflammation: The synergistic role of sphingosine-1-phosphate in COX-2 induction and ceramide-1-phosphate in cPLA(2) binding/translocation.
Pettus, Benjamin James.

Sphingolipids in inflammation: The synergistic role of sphingosine-1-phosphate in COX-2 induction and ceramide-1-phosphate in cPLA(2) binding/translocation. - 217 p.

Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0044.

Thesis (Ph.D.)--Medical University of South Carolina, 2005.

The objective of this study was to identify and characterize the key sphingolipid mediator(s) of cytokine pro-inflammatory pathways (COX-2/cPLA 2) and to identify target mechanism(s) of action for these lipids. This objective necessitated the development of qualitative and quantitatively specific tools for lipid analysis. This led to the development of LC-MS methodologies for ceramide and dihydroceramide species and related metabolites and the application of RNA-interference for sequence-specific gene silencing of upstream and downstream sphingolipid metabolizing enzymes. This work also resulted in the identification of sphingosine-1-phosphate and ceramide-1-phosphate as key sphingolipid mediators of inflammation. Mechanistically, we provide evidence supporting the necessity of the sphingosine kinase 1/sphingosine-1-phosphate pathway in COX-2 induction in response to TNFalpha and IL-1beta. Additionally, evidence supporting the direct interaction between ceramide-1-phosphate with the calcium-lipid binding domain of cPLA2 with resultant calcium-enhanced translocation is shown. Further, evidence supporting the necessity of the ceramide kinase/C1P pathway in cPLA2 translocation and activation in response to agonists is provided. Finally, potent synergy is described between S1P and C1P, each molecule acting on unique intracellular targets, in maximal prostaglandin E2 production. Taken together, these findings implicate the sphingolipids S1P and C1P as key regulators of COX-2 and cPLA2 respectively, with enormous potential relevance to the fields of inflammation and cancer therapeutics.

ISBN: 9780542495946Subjects--Topical Terms:

1017686
Biology, Cell.

Sphingolipids in inflammation: The synergistic role of sphingosine-1-phosphate in COX-2 induction and ceramide-1-phosphate in cPLA(2) binding/translocation.
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100 1 $a Pettus, Benjamin James. $3 1913237
245 1 0 $a Sphingolipids in inflammation: The synergistic role of sphingosine-1-phosphate in COX-2 induction and ceramide-1-phosphate in cPLA(2) binding/translocation.
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500 $a Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0044.
500 $a Adviser: Yusuf A. Hannun.
502 $a Thesis (Ph.D.)--Medical University of South Carolina, 2005.
520 $a The objective of this study was to identify and characterize the key sphingolipid mediator(s) of cytokine pro-inflammatory pathways (COX-2/cPLA 2) and to identify target mechanism(s) of action for these lipids. This objective necessitated the development of qualitative and quantitatively specific tools for lipid analysis. This led to the development of LC-MS methodologies for ceramide and dihydroceramide species and related metabolites and the application of RNA-interference for sequence-specific gene silencing of upstream and downstream sphingolipid metabolizing enzymes. This work also resulted in the identification of sphingosine-1-phosphate and ceramide-1-phosphate as key sphingolipid mediators of inflammation. Mechanistically, we provide evidence supporting the necessity of the sphingosine kinase 1/sphingosine-1-phosphate pathway in COX-2 induction in response to TNFalpha and IL-1beta. Additionally, evidence supporting the direct interaction between ceramide-1-phosphate with the calcium-lipid binding domain of cPLA2 with resultant calcium-enhanced translocation is shown. Further, evidence supporting the necessity of the ceramide kinase/C1P pathway in cPLA2 translocation and activation in response to agonists is provided. Finally, potent synergy is described between S1P and C1P, each molecule acting on unique intracellular targets, in maximal prostaglandin E2 production. Taken together, these findings implicate the sphingolipids S1P and C1P as key regulators of COX-2 and cPLA2 respectively, with enormous potential relevance to the fields of inflammation and cancer therapeutics.
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650 4 $a Biology, Molecular. $3 1017719
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