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Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells

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Abstract

Introduction

In this study, we delineated the apoptotic signaling pathways activated by sodium selenite in NB4 cells.

Materials and methods

NB4 cells were treated with 20 μM sodium selenite for different times. The activation of caspases and ER stress markers, ROS levels, mitochondrial membrane potential and cell apoptosis induced by sodium selenite were analyzed by immunoblotting analysis, DCF fluorescence and flow cytometric respectively. siRNA was used to detect the effect of GADD153 on selenite-induced cell apoptosis.

Conclusions

Sodium selenite-induced reactive oxygen species generation is an early event that triggers endoplasmic reticulum stress mitochondrial apoptotic pathways in NB4 cells.

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Abbreviations

ER:

Endoplasmic reticulum

MnTMPyp:

Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride

ROS:

Reactive oxygen species

UPR:

Unfolded protein response

References

  1. Lavrik IN, Golks A, Krammer PH (2005) Caspases: pharmacological manipulation of cell death. J Clin Invest 115:2665–2672. doi:10.1172/JCI26252

    Article  PubMed  CAS  Google Scholar 

  2. Rutkowski DT, Kaufman RJ (2004) A trip to the ER: coping with stress. Trends Cell Biol 14:20–28. doi:10.1016/j.tcb.2003.11.001

    Article  PubMed  CAS  Google Scholar 

  3. Faitova J, Krekac D, Hrstka R, Vojtesek B (2006) Endoplasmic reticulum stress and apoptosis. Cell Mol Biol Lett 11:488–505. doi:10.2478/s11658-006-0040-4

    Article  PubMed  CAS  Google Scholar 

  4. Szegezdi E, Logue SE, Gorman AM et al (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7:880–885. doi:10.1038/sj.embor.7400779

    Article  PubMed  CAS  Google Scholar 

  5. Zhang KZ, Kaufman RJ (2004) Signaling the unfolded protein response from the endoplasmic reticulum. J Biol Chem 279:25935–25938. doi:10.1074/jbc.R400008200

    Article  PubMed  CAS  Google Scholar 

  6. Kadowaki H, Nishitoh H, Ichijo H (2004) Survival and apoptosis signals in ER stress: the role of protein kinases. J Chem Neuroanat 28:93–100

    PubMed  CAS  Google Scholar 

  7. Wang XZ, Lawson B, Brewer JW et al (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein CHOP/GADD153). Mol Cell Biol 16:4273–4280

    PubMed  CAS  Google Scholar 

  8. Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381–389. doi:10.1038/sj.cdd.4401373

    Article  PubMed  CAS  Google Scholar 

  9. Patrick L (2004) Selenium biochemistry and cancer: a review of the literature. Altern Med Rev 9:239–258

    PubMed  Google Scholar 

  10. Zeng H, Combs GF Jr (2007) Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem 19:1–7. doi:10.1016/j.jnutbio.2007.02.005

    Article  PubMed  CAS  Google Scholar 

  11. Xiang N, Zhao R, Zhong W (2009) Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells. Chemother Pharm 63:351–362

    Article  CAS  Google Scholar 

  12. Gopee NV, Johnson VJ, Sharma RP (2004) Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-δ, nuclear factor-κB, and inhibitor of apoptosis protein. Toxicol Sci 78:204–214. doi:10.1093/toxsci/kfh072

    Article  PubMed  CAS  Google Scholar 

  13. Xiao R, Qiao JT, Zhao HF (2006) Sodium selenite induces apoptosis in cultured cortical neurons with special concomitant changes in expression of the apoptosis-related genes. Neurotoxicology 27:478–484. doi:10.1016/j.neuro.2006.01.008

    Article  PubMed  Google Scholar 

  14. Lanotte M, Martin-Thouvenin V, Najman S et al (1991) NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood 77:1080–1086

    PubMed  CAS  Google Scholar 

  15. Chen Z, Chen CG, Shen ZX et al (2001) Treatment of acute promyelocytic leukemia with arsenic compounds: in vitro and in vivo studies. Semin Hematol 38:26–36. doi:10.1053/shem.2001.20863

    Article  PubMed  CAS  Google Scholar 

  16. Shen ZX, Shi ZZ, Fang J et al (2004) All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA 101:5328–5335. doi:10.1073/pnas.0400053101

    Article  PubMed  CAS  Google Scholar 

  17. Li J, Zuo L, Shen T, Xu CM et al (2003) Induction of apoptosis by sodium selenite in human acute promyelocytic leukemia NB4 cells: involvement of oxidative stress and mitochondria. J Trace Elem Med Biol 17:19–26. doi:10.1016/S0946-672X(03)80041-X

    Article  PubMed  CAS  Google Scholar 

  18. Han BS, Wei W, Hua FY et al (2007) Requirement for ERK activity in sodium selenite-induced apoptosis of acute promyelocytic leukemia-derived NB4 cells. J Biochem Mol Biol 40:196–204

    PubMed  CAS  Google Scholar 

  19. Wu Y, Zhang HT, Dong Y et al (2005) Endoplasmic reticulum stress signal mediators are targets of selenium action. Cancer Res 65:9073–9079. doi:10.1158/0008-5472.CAN-05-2016

    Article  PubMed  CAS  Google Scholar 

  20. Hitomi J, Katayama T, Eguchi Y et al (2004) Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Aβ-induced cell death. J Cell Biol 165:347–356. doi:10.1083/jcb.200310015

    Article  PubMed  CAS  Google Scholar 

  21. Fels DR, Koumenis C (2006) The PERK/eIF2α/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biol Ther 5:723–728. doi:10.1158/1535-7163.MCT-05-0164

    Article  PubMed  CAS  Google Scholar 

  22. Jiang HY, Wek RC (2005) Phosphorylation of the α-subunit of the eukaryotic initiation factor-2α (eIF2α) reduces protein dynthesis and enhances apoptosis in response to proteasome inhibition. J Biol Chem 280:14189–14202. doi:10.1074/jbc.M413660200

    Article  PubMed  CAS  Google Scholar 

  23. Yoshida H, Matsui T, Yamamoto A et al (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891. doi:10.1016/S0092-8674(01)00611-0

    Article  PubMed  CAS  Google Scholar 

  24. Lee AH, Iwakoshi NN, Glimcher LH (2003) XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 23:7448–7459. doi:10.1128/MCB.23.21.7448-7459.2003

    Article  PubMed  CAS  Google Scholar 

  25. Ruddock LW, Molinari M (2006) N-glycan processing in ER quality control. J Cell Sci 119:4373–4380. doi:10.1242/jcs.03225

    Article  PubMed  CAS  Google Scholar 

  26. Zu K, Bihani T, Lin A et al (2006) Enhanced selenium effect on growth arrest by BiP/GRP78 knockdown in p53-null human prostate cancer cells. Oncogene 25:546–554

    PubMed  CAS  Google Scholar 

  27. Hu P, Han Z, Couvillon AD, Exton JH (2004) Critical role of endogenous AKT/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death. J Biol Chem 279:49420–49429. doi:10.1074/jbc.M407700200

    Article  PubMed  CAS  Google Scholar 

  28. Shen HM, Yang CF, Ong CN (1999) Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG2 cells. Int J Cancer 81:820–828. doi:10.1002/(SICI)1097-0215(19990531)81:5<820::AID-IJC25>3.0.CO;2-F

    Article  PubMed  CAS  Google Scholar 

  29. Li GX, Hu H, Jiang C, Schuster T (2007) Differential involvement of reactive oxygen species in apoptosis induced by two classes of selenium compounds in human prostate cancer cells. Int J Cancer 120:2034–2043. doi:10.1002/ijc.22480

    Article  PubMed  CAS  Google Scholar 

  30. Karen DM, Jennifer LM, Lars-oliver K et al (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating bcl2 and perturbing the cellular redox state. Mol Cell Biol 21:1249–1259. doi:10.1128/MCB.21.4.1249-1259.2001

    Article  Google Scholar 

  31. Kuo CT, Hsu MJ, Chen BC et al (2008) Denbinobin induces apoptosis in human lung adenocarcinoma cells via Akt inactivation, bad activation, and mitochondrial dysfunction. Toxicol Lett 177:48–58

    PubMed  CAS  Google Scholar 

  32. Nobumichi O, Satoshi Y, Takayuki H (2005) TRB3, a novel ER stress-inducible gene, is induced via ATF4–CHOP pathway and is involved in cell death. EMBO J 24:1243–1255. doi:10.1038/sj.emboj.7600596

    Article  Google Scholar 

  33. Kato S, Du K (2007) TRB3 modulates C2C12 differentiation by interfering with AKT activation. Biochem Biophys Res Commun 353:933–938. doi:10.1016/j.bbrc.2006.12.161

    Article  PubMed  CAS  Google Scholar 

  34. Xue X, Piao JH, Nakajima A et al (2005) Tumor necrosis factor-α (TNF-α) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNF-α. J Biol Chem 280:33917–33925. doi:10.1074/jbc.M505818200

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from National Natural Sciences Foundation of China (no. 30370348 and no. 30770491), Doctoral Point Foundation of National Educational Committee (no. 20010023029), and Natural Sciences Foundation of Beijing (no. 7032034 and no. 5082015).

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Authors and Affiliations

  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medicine Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

    Liying Guan, Binshe Han, Zhushi Li, Fangyuan Hua, Fang Huang, Wei Wei, Yang Yang & Caimin Xu

  2. Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

    Liying Guan

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  1. Liying Guan
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Correspondence to Liying Guan.

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Guan, L., Han, B., Li, Z. et al. Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells. Apoptosis 14, 218–225 (2009). https://doi.org/10.1007/s10495-008-0295-5

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