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International Journal of Molecular Medicine
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April 2013 Volume 31 Issue 4

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International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Article

Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling

  • Authors:
    • You-Jin Lee
    • Jae-Kyo Jeong
    • Ju-Hee Lee
    • Yang-Gyu Park
    • Ji-Hong Moon
    • Jae-Won Seol
    • Christopher J. Jackson
    • Sang-Youel Park
  • View Affiliations / Copyright

    Affiliations: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea, Institute of Bone and Joint Research, University of Sydney, Kolling Institute, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
  • Pages: 811-816
    |
    Published online on: February 4, 2013
       https://doi.org/10.3892/ijmm.2013.1266
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Abstract

Bisphosphonates (BPs) remain the most widely used and effective antiresorptive agents in the treatment of postmenopausal osteoporosis. In particular, nitrogen-containing BPs (N-BPs) are more potent at inhibiting bone resorption in vivo than simple BPs, but they are associated with a number of side-effects including increased endothelial cell apoptosis in patients with multiple myeloma. Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, plays important roles in the regulation of cell growth, differentiation and programmed cell death as a multifunctional bioactive lipid mediator. The aim of this study was to elucidate the protective effect and the possible mechanism of S1P against BP-induced cell damage using human umbilical vein endothelial cells (HUVECs). HUVECs were treated with S1P for 1 h and then with BP including alendronate, zoledronate and risedronate. S1P protects HUVECs against BP-induced cell death and the protective effect was increased by S1P in a dose-dependent manner. S1P blocked BP-induced caspase-3 activation, nuclear factor-κB activation, c-Jun-N-terminal kinase (JNK) phosphorylation and DNA fragmentation. The blocking of JNK phosphorylation inhibited BP-induced caspase activation and HUVEC cell death. The present study demonstrates that S1P inhibits BP-induced endothelial cell death via regulation of JNK phosphorylation, and also suggests that S1P has the potential to be a therapeutic drug in various vascular diseases induced by BP.
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1 

Roelofs AJ, Thompson K, Gordon S and Rogers MJ: Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res. 12:6222s–6230s. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Allegra A, Alonci A, Penna G, et al: Bisphosphonates induce apoptosis of circulating endothelial cells in multiple myeloma patients and in subjects with bisphosphonate-induced osteonecrosis of the jaws. Acta Haematol. 124:79–85. 2010. View Article : Google Scholar

3 

Tassone P, Tagliaferri P, Viscomi C, et al: Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro. Br J Cancer. 88:1971–1978. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Hashimoto K, Morishige K, Sawada K, et al: Alendronate suppresses tumor angiogenesis by inhibiting Rho activation of endothelial cells. Biochem Biophys Res Commun. 354:478–484. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Fu L, Tang T, Miao Y, Zhang S, Qu Z and Dai K: Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. Bone. 43:40–47. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Inoue R, Matsuki NA, Jing G, Kanematsu T, Abe K and Hirata M: The inhibitory effect of alendronate, a nitrogen-containing bisphosphonate on the PI3K-Akt-NFkappaB pathway in osteosarcoma cells. Br J Pharmacol. 146:633–641. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Hasmim M, Bieler G and Ruegg C: Zoledronate inhibits endothelial cell adhesion, migration and survival through the suppression of multiple, prenylation-dependent signaling pathways. J Thromb Haemost. 5:166–173. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Tsai SH, Huang PH, Chang WC, et al: Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells. PLoS One. 7:e410652012. View Article : Google Scholar : PubMed/NCBI

9 

Maceyka M, Harikumar KB, Milstien S and Spiegel S: Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol. 22:50–60. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Morales-Ruiz M, Lee MJ, Zollner S, et al: Sphingosine 1-phosphate activates Akt, nitric oxide production, and chemotaxis through a Gi protein/phosphoinositide 3-kinase pathway in endothelial cells. J Biol Chem. 276:19672–19677. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Ishii M and Kikuta J: Sphingosine-1-phosphate signaling controlling osteoclasts and bone homeostasis. Biochim Biophys Acta. 1831:223–227. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Kimura T, Sato K, Kuwabara A, et al: Sphingosine 1-phosphate may be a major component of plasma lipoproteins responsible for the cytoprotective actions in human umbilical vein endothelial cells. J Biol Chem. 276:31780–31785. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Seol JW, Lee YJ, Jackson CJ, Sambrook PN and Park SY: Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways. Int J Mol Med. 27:835–840. 2011.PubMed/NCBI

14 

Wolf AM, Rumpold H, Tilg H, Gastl G, Gunsilius E and Wolf D: The effect of zoledronic acid on the function and differentiation of myeloid cells. Haematologica. 91:1165–1171. 2006.PubMed/NCBI

15 

Russell RG, Watts NB, Ebetino FH and Rogers MJ: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 19:733–759. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Rogers MJ, Russell RG, Blackburn GM, Williamson MP and Watts DJ: Metabolism of halogenated bisphosphonates by the cellular slime mould Dictyostelium discoideum. Biochem Biophys Res Commun. 189:414–423. 1992. View Article : Google Scholar : PubMed/NCBI

17 

Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G and Rogers MJ: Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 13:581–589. 1998. View Article : Google Scholar

18 

Luckman SP, Coxon FP, Ebetino FH, Russell RG and Rogers MJ: Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages. J Bone Miner Res. 13:1668–1678. 1998. View Article : Google Scholar

19 

Perez-Sala D and Mollinedo F: Inhibition of isoprenoid biosynthesis induces apoptosis in human promyelocytic HL-60 cells. Biochem Biophys Res Commun. 199:1209–1215. 1994. View Article : Google Scholar : PubMed/NCBI

20 

Yatomi Y, Igarashi Y, Yang L, et al: Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serum. J Biochem. 121:969–973. 1997. View Article : Google Scholar : PubMed/NCBI

21 

Limaye V, Li X, Hahn C, et al: Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members. Blood. 105:3169–3177. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Kumar A, Byun HS, Bittman R and Saba JD: The sphingolipid degradation product trans-2-hexadecenal induces cytoskeletal reorganization and apoptosis in a JNK-dependent manner. Cell Signal. 23:1144–1152. 2011.

23 

Dunford JE, Rogers MJ, Ebetino FH, Phipps RJ and Coxon FP: Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. J Bone Miner Res. 21:684–694. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lee Y, Jeong J, Lee J, Park Y, Moon J, Seol J, Jackson CJ and Park S: Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling. Int J Mol Med 31: 811-816, 2013.
APA
Lee, Y., Jeong, J., Lee, J., Park, Y., Moon, J., Seol, J. ... Park, S. (2013). Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling. International Journal of Molecular Medicine, 31, 811-816. https://doi.org/10.3892/ijmm.2013.1266
MLA
Lee, Y., Jeong, J., Lee, J., Park, Y., Moon, J., Seol, J., Jackson, C. J., Park, S."Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling". International Journal of Molecular Medicine 31.4 (2013): 811-816.
Chicago
Lee, Y., Jeong, J., Lee, J., Park, Y., Moon, J., Seol, J., Jackson, C. J., Park, S."Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling". International Journal of Molecular Medicine 31, no. 4 (2013): 811-816. https://doi.org/10.3892/ijmm.2013.1266
Copy and paste a formatted citation
x
Spandidos Publications style
Lee Y, Jeong J, Lee J, Park Y, Moon J, Seol J, Jackson CJ and Park S: Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling. Int J Mol Med 31: 811-816, 2013.
APA
Lee, Y., Jeong, J., Lee, J., Park, Y., Moon, J., Seol, J. ... Park, S. (2013). Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling. International Journal of Molecular Medicine, 31, 811-816. https://doi.org/10.3892/ijmm.2013.1266
MLA
Lee, Y., Jeong, J., Lee, J., Park, Y., Moon, J., Seol, J., Jackson, C. J., Park, S."Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling". International Journal of Molecular Medicine 31.4 (2013): 811-816.
Chicago
Lee, Y., Jeong, J., Lee, J., Park, Y., Moon, J., Seol, J., Jackson, C. J., Park, S."Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling". International Journal of Molecular Medicine 31, no. 4 (2013): 811-816. https://doi.org/10.3892/ijmm.2013.1266
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