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Activation of telomerase and cyclooxygenase-2 in PDGF and FGF inhibition of C2-ceramide-induced apoptosis.
J Cell Physiol. 2009 Feb; 218(2):405-15.JC

Abstract

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.

Authors+Show Affiliations

Division of Nephrology, Chi Mei Medical Center, Tainan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18932216

Citation

Chien, Chih-Chiang, et al. "Activation of Telomerase and Cyclooxygenase-2 in PDGF and FGF Inhibition of C2-ceramide-induced Apoptosis." Journal of Cellular Physiology, vol. 218, no. 2, 2009, pp. 405-15.
Chien CC, Shen SC, Yang LY, et al. Activation of telomerase and cyclooxygenase-2 in PDGF and FGF inhibition of C2-ceramide-induced apoptosis. J Cell Physiol. 2009;218(2):405-15.
Chien, C. C., Shen, S. C., Yang, L. Y., Wu, C. Y., Liau, J. S., & Chen, Y. C. (2009). Activation of telomerase and cyclooxygenase-2 in PDGF and FGF inhibition of C2-ceramide-induced apoptosis. Journal of Cellular Physiology, 218(2), 405-15. https://doi.org/10.1002/jcp.21613
Chien CC, et al. Activation of Telomerase and Cyclooxygenase-2 in PDGF and FGF Inhibition of C2-ceramide-induced Apoptosis. J Cell Physiol. 2009;218(2):405-15. PubMed PMID: 18932216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of telomerase and cyclooxygenase-2 in PDGF and FGF inhibition of C2-ceramide-induced apoptosis. AU - Chien,Chih-Chiang, AU - Shen,Shing-Chuan, AU - Yang,Liang-Yo, AU - Wu,Chin-Yen, AU - Liau,Jiun-Shiang, AU - Chen,Yen-Chou, PY - 2008/10/22/pubmed PY - 2008/12/18/medline PY - 2008/10/22/entrez SP - 405 EP - 15 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 218 IS - 2 N2 - 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. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/18932216/Activation_of_telomerase_and_cyclooxygenase_2_in_PDGF_and_FGF_inhibition_of_C2_ceramide_induced_apoptosis_ L2 - https://doi.org/10.1002/jcp.21613 DB - PRIME DP - Unbound Medicine ER -