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Published in: Hepatology International 1/2015

01-01-2015 | Original Article

FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, protects sinusoid endothelial cells from radiation injury in vitro

Authors: Shu-Min Zhang, Yi-Xing Chen, Jing Sun, Lei Guo, Zhao-Chong Zeng

Published in: Hepatology International | Issue 1/2015

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Abstract

Purpose

To determine whether FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, would protect sinusoid endothelial cells (SECs) from radiation injury in vitro.

Materials and methods

The effect of FTY720 on the viability of irradiated human liver SECs were examined by MTT assay or FACS analysis. The effect of FTY720 on the survival of hepatocellular carcinoma cell line, HepG2 and McA-RH7777, were determined by clonogenic assays. The activation of Akt pathway was tested by western bolt.

Results

FTY720 increases the survival of irradiated SECs; in contrast, it does not appear to be radioprotective of tumor cells. Furthermore, the activation of Akt pathway was confirmed in the protective effect of FTY720 on SECs.

Conclusion

These results suggest that FTY720 will be a potential therapeutic protector for the SEC apoptosis during RILD.
Literature
1.
go back to reference Lawrence TS, Robertson JM, Anscher MS, et al. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 1995;31(5):1237–1248 Lawrence TS, Robertson JM, Anscher MS, et al. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 1995;31(5):1237–1248
2.
go back to reference Alati T, Eckl P, Jirtle RL. An in vitro micronucleus assay for determining the radiosensitivity of hepatocytes. Radiat Res 1989;119(3):562–568 Alati T, Eckl P, Jirtle RL. An in vitro micronucleus assay for determining the radiosensitivity of hepatocytes. Radiat Res 1989;119(3):562–568
3.
go back to reference Alati T, Van Cleeff M, Strom SC, et al. Radiation sensitivity of adult human parenchymal hepatocytes. Radiat Res 1988;115(1):152–160 Alati T, Van Cleeff M, Strom SC, et al. Radiation sensitivity of adult human parenchymal hepatocytes. Radiat Res 1988;115(1):152–160
4.
go back to reference Jirtle RL, DeLuca PM, Hinshaw WM, et al. Survival of parenchymal hepatocytes irradiated with 14.3 MeV neutrons. Int J Radiat Oncol Biol Phys 1984;10(6):895–899 Jirtle RL, DeLuca PM, Hinshaw WM, et al. Survival of parenchymal hepatocytes irradiated with 14.3 MeV neutrons. Int J Radiat Oncol Biol Phys 1984;10(6):895–899
5.
go back to reference Jirtle RL, Michalopoulos G, McLain JR, et al. Transplantation system for determining the clonogenic survival of parenchymal hepatocytes exposed to ionizing radiation. Cancer Res 1981;41(9 Pt 1):3512–3518 Jirtle RL, Michalopoulos G, McLain JR, et al. Transplantation system for determining the clonogenic survival of parenchymal hepatocytes exposed to ionizing radiation. Cancer Res 1981;41(9 Pt 1):3512–3518
6.
go back to reference Jirtle RL, Michalopoulos G, Strom SC, et al. The survival of parenchymal hepatocytes irradiated with low and high LET radiation. Br J Cancer Suppl 1984;6:197–201 Jirtle RL, Michalopoulos G, Strom SC, et al. The survival of parenchymal hepatocytes irradiated with low and high LET radiation. Br J Cancer Suppl 1984;6:197–201
7.
go back to reference Reed GB Jr., Cox AJ Jr. The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol 1966;48(4):597–611 Reed GB Jr., Cox AJ Jr. The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol 1966;48(4):597–611
8.
go back to reference Fajardo LF, Colby TV. Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med 1980;104(11):584–588 Fajardo LF, Colby TV. Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med 1980;104(11):584–588
9.
go back to reference Yamanouchi K, Zhou H, Roy-Chowdhury N, et al. Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation. Hepatology 2009;49(1):258–267 Yamanouchi K, Zhou H, Roy-Chowdhury N, et al. Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation. Hepatology 2009;49(1):258–267
10.
go back to reference Sun X, Shikata Y, Wang L, et al. Enhanced interaction between focal adhesion and adherens junction proteins: involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. Microvasc Res 2009;77(3):304–313 Sun X, Shikata Y, Wang L, et al. Enhanced interaction between focal adhesion and adherens junction proteins: involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. Microvasc Res 2009;77(3):304–313
11.
go back to reference Moriue T, Igarashi J, Yoneda K, et al. Sphingosine 1-phosphate attenuates H2O2-induced apoptosis in endothelial cells. Biochem Biophys Res Commun 2008;368(4):852–857 Moriue T, Igarashi J, Yoneda K, et al. Sphingosine 1-phosphate attenuates H2O2-induced apoptosis in endothelial cells. Biochem Biophys Res Commun 2008;368(4):852–857
12.
go back to reference Zheng DM, Kitamura T, Ikejima K, et al. Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: role of intracellular calcium and nitric oxide. Hepatology 2006;44(5):1278–1287 Zheng DM, Kitamura T, Ikejima K, et al. Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: role of intracellular calcium and nitric oxide. Hepatology 2006;44(5):1278–1287
13.
go back to reference Kwon YG, Min JK, Kim KM, et al. Sphingosine 1-phosphate protects human umbilical vein endothelial cells from serum-deprived apoptosis by nitric oxide production. J Biol Chem 2001;276(14):10627–10633 Kwon YG, Min JK, Kim KM, et al. Sphingosine 1-phosphate protects human umbilical vein endothelial cells from serum-deprived apoptosis by nitric oxide production. J Biol Chem 2001;276(14):10627–10633
14.
go back to reference Bonnaud S, Niaudet C, Pottier G, et al. Sphingosine-1-phosphate protects proliferating endothelial cells from ceramide-induced apoptosis but not from DNA damage-induced mitotic death. Cancer Res 2007;67(4):1803–18011 Bonnaud S, Niaudet C, Pottier G, et al. Sphingosine-1-phosphate protects proliferating endothelial cells from ceramide-induced apoptosis but not from DNA damage-induced mitotic death. Cancer Res 2007;67(4):1803–18011
15.
go back to reference Bonnaud S, Niaudet C, Legoux F, et al. Sphingosine-1-phosphate activates the AKT pathway to protect small intestines from radiation-induced endothelial apoptosis. Cancer Res 2010;70(23):9905–9915 Bonnaud S, Niaudet C, Legoux F, et al. Sphingosine-1-phosphate activates the AKT pathway to protect small intestines from radiation-induced endothelial apoptosis. Cancer Res 2010;70(23):9905–9915
16.
go back to reference Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003;22(37):5897–5906 Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003;22(37):5897–5906
17.
go back to reference Natarajan V, Dudek SM, Jacobson JR, et al. Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury. Am J Respir Cell Mol Biol 2013;49(1):6–17 Natarajan V, Dudek SM, Jacobson JR, et al. Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury. Am J Respir Cell Mol Biol 2013;49(1):6–17
18.
go back to reference Stessin AM, Gursel DB, Schwartz A, et al. FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells. Neurosci Lett 2012;516(2):253–258 Stessin AM, Gursel DB, Schwartz A, et al. FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells. Neurosci Lett 2012;516(2):253–258
19.
go back to reference Vainshtein JM, Kabarriti R, Mehta KJ, et al. Bone marrow-derived stromal cell therapy in cirrhosis: clinical evidence, cellular mechanisms, and implications for the treatment of hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2014;89(4):786–803 Vainshtein JM, Kabarriti R, Mehta KJ, et al. Bone marrow-derived stromal cell therapy in cirrhosis: clinical evidence, cellular mechanisms, and implications for the treatment of hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2014;89(4):786–803
20.
go back to reference Harada J, Foley M, Moskowitz MA, et al. Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. J Neurochem 2004;88(4):1026–1039 Harada J, Foley M, Moskowitz MA, et al. Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. J Neurochem 2004;88(4):1026–1039
21.
go back to reference Kimura A, Ohmori T, Ohkawa R, et al. Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 2007;25(1):115–124 Kimura A, Ohmori T, Ohkawa R, et al. Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 2007;25(1):115–124
22.
go back to reference Mizugishi K, Yamashita T, Olivera A, et al. Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 2005;25(24):11113–11121 Mizugishi K, Yamashita T, Olivera A, et al. Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 2005;25(24):11113–11121
23.
go back to reference Mathew B, Jacobson JR, Berdyshev E, et al. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. FASEB J 2011;25(10):3388–3400 Mathew B, Jacobson JR, Berdyshev E, et al. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. FASEB J 2011;25(10):3388–3400
24.
go back to reference Morita Y, Perez GI, Paris F, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med 2000;6(10):1109–1114 Morita Y, Perez GI, Paris F, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med 2000;6(10):1109–1114
25.
go back to reference Roninson IB, Broude EV, Chang BD. If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resist Updates 2001;4(5):303–313 Roninson IB, Broude EV, Chang BD. If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resist Updates 2001;4(5):303–313
26.
go back to reference Hannun YA. Functions of ceramide in coordinating cellular responses to stress. Science 1996;274(5294):1855–1859 Hannun YA. Functions of ceramide in coordinating cellular responses to stress. Science 1996;274(5294):1855–1859
27.
go back to reference Edwards E, Geng L, Tan J, et al. Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation. Cancer Res 2002;62(16):4671–4677 Edwards E, Geng L, Tan J, et al. Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation. Cancer Res 2002;62(16):4671–4677
Metadata
Title
FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, protects sinusoid endothelial cells from radiation injury in vitro
Authors
Shu-Min Zhang
Yi-Xing Chen
Jing Sun
Lei Guo
Zhao-Chong Zeng
Publication date
01-01-2015
Publisher
Springer India
Published in
Hepatology International / Issue 1/2015
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-014-9590-0

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