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神经酰胺对人内皮细胞凋亡及bax、bcl-2表达的影响 被引量:1

Effects of ceramide on apoptosis of human endothelial cells and expressions of bcl-2 and bax
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摘要 目的观察外源性神经酰胺(C2-ceramide)对内皮细胞凋亡及相关基因bax和bcl-2表达变化的影响。方法原代培养人脐静脉血管内皮细胞,加药组加入终浓度分别为5、12.5、25、50μmol/L的C2-ceramide,对照组加入体积分数为0.1%的无水乙醇。采用TUNEL法检测细胞凋亡,用RT-PCR、Western blot技术对bax mRNA、bcl-2mRNA及蛋白表达进行分析。结果加药组内皮细胞的凋亡阳性率显著高于对照组(P<0.05),且具有时间和剂量依赖性;加药组baxmRNA及蛋白的表达较对照组显著升高(P<0.05),bcl-2mRNA及蛋白的表达较对照组则显著降低(P<0.05)。结论外源性神经酰胺通过上调bax及下调bcl-2表达水平,改变bax/bcl-2值,从而诱导内皮细胞凋亡。 Objective To observe the effect of ceramide on apoptosis of endothelial cells (EC) and deter- mine the relationship between the ceramide-induced growth suppression and the expressions of bax and bcl-2. Methods Human umbilical endothelial cells were cultured in vitro and treated with 5, 12.5, 25, 50 μmoL/L C2-ceramide, the cells treated with absolute alcohol as control. TUNEL was employed to determine the apoptosis of the cultured EC. Bax and bcl-2 mRNA and protein levels of EC were detected by RT-PCR and Western blot. Results The number of apoptotic cells was significantly higher in ceramide-treated endothelial cells than that in the control group (P 〈 0. 05 ). Ceramide-induced EC apopotsis was in time- and dose-dependent manner. Compared with the control cells, the expressions of bax mRNA and protein in EC treated with ceramide significantly increased (P 〈 0. 05 ) , while the expressions of bcl-2 mRNA and protein significantly depressed ( P 〈 0. 05). Conclusion Ceramide may induce apoptosis of endothelial cells by down-regulating bcl-2 and up-regulating bax.
出处 《第三军医大学学报》 CAS CSCD 北大核心 2008年第10期957-959,共3页 Journal of Third Military Medical University
关键词 神经酰胺 内皮细胞 凋亡 BAX BCL-2 ceramide endothelial cells apoptosis bax bcl-2
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参考文献11

  • 1Ohanian J, Ohanian V. Sphingolipids in mammalian cell signalling [J]. Cell Mol Life Sci, 2001,58(14) : 2053 -2068.
  • 2Ruvolo P P. Ceramide regulates cellular homeostasis via diverse stress signaling pathways [J]. Leukemia, 2001, 15 (8): 1153-1160.
  • 3Madan B, Singh I, Kumar A, et al. Xanthones as inhibitors of microsomal lipid peroxidation and TNF-alpha induced ICAM-1 expression on human umbilical vein endothelial cells (HUVECs) [ J]. Bioorg Med Chem, 2002, 10(11 ) : 3431 -3436.
  • 4Bonavita F, Stefanelli C, Giordano E, et al. H9c2 cardiac myoblasts undergo apoptosis in a model of ischemia consisting of serum deprivation and hypoxia: inhibition by PMA [J]. FEBS Lett, 2003, 536 (1 -3) : 85 -91.
  • 5Wassmann S, Nickenig G. Pathophysiological regulation of the AT1 -receptor and implications for vascular disease [ ] ]. J Hypertens Suppl, 2006, 24(1) : S15 -S21.
  • 6Obeid L M, Linardic C M, Karolak L A, et al. Programmed cell death induced by ceramide[ J]. Science, 1993, 259(5102) : 1769 -1771.
  • 7Lee J U, Hosotani R, Wada M, et al. Role of Bel-2 family proteins (Box, Bel-2 and Bel-X) on cellular susceptibility to radiation pancreatic cancer cells[J]. Eur J Cancer, 1999, 35 (9): 1374-1380.
  • 8Kim S S, Chae H S, Bach J H, et al. p53 mediates ceramide-induced apoptosis in SKN-SH cells [J]. Oncogene, 20112, 21(13) : 2020 -21128.
  • 9Kim H J, Mun J Y, Chun Y J, et al. Bax-dependent apoptosis induced by oeramide in HL-60 cells[J], FEBS Lett, 2001,505(2) : 264 -268.
  • 10Yang H, Sadda M R, Li M, et al. S-adenosylmethionine and its metabolite induce apoptosis in HepG2 cells: Role of protein phosphatase 1 and Bcl-x(S)[J]. Hepatology, 2004, 40(1) : 221 -231.

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  • 1Pui C H, Evans W E. Treatment of acute lymphoblastic leukemia[ J]. N Engl J Med, 2006, 354(2) : 166 -178.
  • 2Leone G, Sica S, Voso M T, et al. Treatment of acute leukaemias with monoclonal antibodies: current status and future prospects[ J]. Cardiovasc Hematol Agents Med Chem, 2006, 4( 1 ) : 33 -52.
  • 3Direkze N C, Jeffery R, Hodivala-Dilke K, et al. Bone marrow-derived stromal ceils express lineage-related messenger RNA speeies[J]. Cancer Res, 2006, 66(3): 1265- 1269.
  • 4Gao L, Chen X H, Zhang X, et al. Human umbilical cord blood-derived stromal cell, a new resource of feeder layer to expand human umbilical cord blood CD34^+ cells in vitro [ J ]. Blood Ceils Mol Dis, 2006, 36(2) : 322 -328.
  • 5Correl J, Mahtouk K, Attal M, et al. Bone marrow mesenchymal stem cells are abnormal in muhiple myeloma [ J ]. Leukemia, 2007,21 ( 5 ) : 1079 - 1088.
  • 6Anderson K C. Targeted therapy of muhiple myeloma based upon tumor-microenvironmental interactions[ J ]. Exp Hematol, 2007, 35 (4 Suppl 1 ) : 155 - 162.
  • 7Wang L H, Yang X Y, Zhang X, et al. Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPARgamma cross talk with NF-kappaB and C/EBP [ J ]. Blood, 2007, 110(13) : 4373 -4384.
  • 8Ge Y, Zhan F, Barlogie B, et al. Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival [J]. Br J Haematol, 2006, 133( 1 ) : 83 -92.
  • 9Mitsiades C S, Mitsiades N S, Munshi N C, et al. The role of the bone microenvironment in the pathophysiology and therapeutic management of multiple myeloma: interplay of growth factors, their receptors and stromal interactions [ J]. Eur J Cancer 2006, 42 ( 11 ) : 1564 - 1573.
  • 10Nefedova Y, Landowski T H, Dalton W S. Bone marrow stromal-derived soluble factors and direct cells contact contribute to de novo drug resistance of myeloma cells by distinct mechanisms [ J ]. Leukemia, 2003, 17(6) : 1175 -1182.

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