Document Detail

Activation of telomerase and cyclooxygenase-2 in PDGF and FGF inhibition of C2-ceramide-induced apoptosis.
MedLine Citation:
PMID:  18932216     Owner:  NLM     Status:  MEDLINE    
In the present study, the roles of telomerase and prostaglandin E(2) (PGE(2)) in platelet-derived growth factor (PDGF's) and fibroblast growth factor-2 (FGF-2's) effects against C(2)-ceramide-induced cell death were investigated. C(2)-ceramide reduced the viability of NIH3T3 cells in a condition without calf serum (CS) in accordance with decreasing telomerase activity according to the TRAP assay. The addition of CS significantly protected cells from C(2)-ceramide-induced apoptosis through increased telomerase activity, and the phosphorylations of PDGF and the FGF-2-like receptor in NIH3T3 cells were detected. Adding PDGF and FGF-2 decreased the cytotoxic effect elicited by C(2)-ceramide through stimulating telomerase activity, which was blocked by adding a telomerase inhibitor (TI). Activations of ERKs and JNKs were detected in PDGF- and FGF-2-treated NIH3T3 cells, and the telomerase activities induced by PDGF and FGF were respectively inhibited by the addition of the ERK inhibitor, PD98059, and the JNK inhibitor, SP600125. Accordingly, induction of cyclooxygenase-2 (COX-2) protein expression and PGE(2) production was detected in PDGF- and FGF-2-treated NIH3T3 cells, and the telomerase activities stimulated by PDGF and FGF were reduced by adding a specific COX-2 inhibitor, NS398, through a decrease in PGE(2) production. Incubation of cells with PGE(2) or the EP1 agonist, 17-PT, but not the EP2 agonist, sulprostone, the EP3 agonist, butaprost, or the EP4 agonist, PGE(1) alcohol, significantly enhanced the telomerase activity of NIH3T3 cells. PGE(2) protection of NIH3T3 cells against C(2)-ceramide-induced cell death was identified by the MTT and LDH-release assays, and it was inhibited by adding the EP1 antagonist, SC-19220. Ceramide metabolites including ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P), and a standard control of exogenous ceramide C(2)-dihydroceramide show no effect on the telomerase activity and viability of NIH3T3 cells. The involvement of COX-2/PGE(2)-mediated telomerase activation by PDGF and FGF-2 against C(2)-ceramide-induced cell death is first demonstrated herein.
Chih-Chiang Chien; Shing-Chuan Shen; Liang-Yo Yang; Chin-Yen Wu; Jiun-Shiang Liau; Yen-Chou Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  218     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2008-12-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-15     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Division of Nephrology, Chi Mei Medical Center, Tainan, Taiwan.
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MeSH Terms
Apoptosis / drug effects*
Cell Survival / drug effects
Ceramides / pharmacology
Cyclooxygenase 2 / metabolism*
Cytoprotection / drug effects
Dinoprostone / biosynthesis
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / metabolism
Fibroblast Growth Factor 2 / pharmacology*
JNK Mitogen-Activated Protein Kinases / metabolism
Lysophospholipids / pharmacology
NIH 3T3 Cells
Phosphorylation / drug effects
Platelet-Derived Growth Factor / pharmacology*
Sphingosine / analogs & derivatives*,  pharmacology
Telomerase / metabolism*
Reg. No./Substance:
0/Ceramides; 0/Enzyme Inhibitors; 0/Lysophospholipids; 0/N-acetylsphingosine; 0/Platelet-Derived Growth Factor; 0/ceramide 1-phosphate; 0/dihydroceramide; 103107-01-3/Fibroblast Growth Factor 2; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 363-24-6/Dinoprostone; EC 1.14.99.-/Ptgs2 protein, mouse; EC 2; EC Signal-Regulated MAP Kinases; EC Mitogen-Activated Protein Kinases; EC

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