Tamoxifen induces apoptosis of mouse microglia cell line BV-2 cells via both mitochondrial and death receptor pathways

Zhengwei Li , Jincao Chen , Ting Lei , Huaqiu Zhang

Current Medical Science ›› 2012, Vol. 32 ›› Issue (2) : 221 -226.

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Current Medical Science ›› 2012, Vol. 32 ›› Issue (2) : 221 -226. DOI: 10.1007/s11596-012-0039-1
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Tamoxifen induces apoptosis of mouse microglia cell line BV-2 cells via both mitochondrial and death receptor pathways

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Abstract

Little is known about whether tamoxifen (TAM) can affect resting state microglia apoptosis and about the cellular mechanism that may account for this. To explore this question, we incubated the microglia cell line BV-2 cells with TAM at different concentrations. Cell viability was assessed by the MTT assay, and flow cytometric analysis was performed to detect the cell apoptosis rate. Furthermore, mitochondrial membrane potential (Δψm) was tested by flow cytometry, and Bax, Bcl-2, Fas, and Fas-L expression was detected by Western blot. The results demonstrated that TAM decreased cell viability and induced apoptosis of BV-2 cells in a concentration- and time-dependent manner. In addition, disruption of Δψm was followed by up-regulated expression of pro-apoptotic Bax, Fas and Fas-L, and down-regulated expression of anti-apoptotic Bcl-2. These results indicate that TAM may induce apoptosis of BV-2 cells through both mitochondria- and death receptor-mediated pathways.

Keywords

microglia / BV-2 cells / apoptosis / tamoxifen / mitochondria / death receptor

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Zhengwei Li, Jincao Chen, Ting Lei, Huaqiu Zhang. Tamoxifen induces apoptosis of mouse microglia cell line BV-2 cells via both mitochondrial and death receptor pathways. Current Medical Science, 2012, 32(2): 221-226 DOI:10.1007/s11596-012-0039-1

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References

[1]

KarnA., JhaA.K., ShresthaS., et al.. Tamoxifen for breast cancer. JNMA, 2010, 49(177): 62-67

[2]

LoveR.R.. Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects. J Clin Oncol, 1989, 7(6): 803-815

[3]

IsmailogluO., OralB., GorguluA., et al.. Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats. J Clin Neurosci, 2010, 17(10): 1306-1310

[4]

SchlichterL.C., MertensT., LiuB.. Swelling activated Cl channels in microglia: Biophysics, pharmacology and role in glutamate release. Channels (Austin), 2011, 5(2): 128-137

[5]

ZhangH.Q., CaoH.J., KimelbergH.K., et al.. Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death. PLoS One, 2011, 6(2): e16803

[6]

LiuJ.L., TianD.S., LiZ.W., et al.. Tamoxifen alleviates irradiation-induced brain injury by attenuating microglial inflammatory response in vitro and in vivo. Brain Res, 2010, 1316: 101-111

[7]

LeoneD.P., GenoudS., AtanasoskiS., et al.. Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells. Mol Cell Neurosci, 2003, 22(4): 430-440

[8]

ZhangH.Q., XieM.J., SchoolsG.P., et al.. Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model. Brain Res, 2009, 1247: 196-211

[9]

GraeberM.B.. Changing face of microglia. Science, 2010, 330(6005): 783-788

[10]

NimmerjahnA., KirchhoffF., HelmchenF.. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science, 2005, 308(5726): 1314-1318

[11]

HinesD.J., HinesR.M., MulliganS.J., et al.. Microglia processes block the spread of damage in the brain and require functional chloride channels. Glia, 2009, 57(15): 1610-1618

[12]

KjaerK., StrobaekD., ChristophersenP., et al.. Chloride channel blockers inhibit iNOS expression and NO production in IFNgamma-stimulated microglial BV2 cells. Brain Res, 2009, 1281: 15-24

[13]

FengY., HuangJ., DingY., et al.. Tamoxifen-induced apoptosis of rat C6 glioma cells via PI3K/Akt, JNK and ERK activation. Oncol Rep, 2010, 24(6): 1561-1567

[14]

KallioA., ZhengA., DahllundJ., et al.. Role of mitochondria in tamoxifen-induced rapid death of MCF-7 breast cancer cells. Apoptosis, 2005, 10(6): 1395-1410

[15]

NagarkattiN., DavisB.A.. Tamoxifen induces apoptosis in Fas+ tumor cells by upregulating the expression of Fas ligand. Cancer Chemother Pharmacol, 2003, 51(4): 284-290

[16]

MandlekarS., KongA.N.. Mechanisms of tamoxifen-induced apoptosis. Apoptosis, 2001, 6(6): 469-477

[17]

GuoR., HuangZ., ShuY., et al.. Tamoxifen inhibits proliferation and induces apoptosis in human hepatocellular carcinoma cell line HepG2 via down-regulation of survivin expression. Biomed Pharmacother, 2009, 63(5): 375-379

[18]

NagaharaY., ShiinaI., NakataK., et al.. Induction of mitochondria-involved apoptosis in estrogen receptor-negative cells by a novel tamoxifen derivative, ridaifen-B. Cancer Sci, 2008, 99(3): 608-614

[19]

SimardM., ZhangW., HintonD.R., et al.. Tamoxifen-induced growth arrest and apoptosis in pituitary tumor cells in vitro via a protein kinase C-independent pathway. Cancer Lett, 2002, 185(2): 131-138

[20]

GreenD.R.. Apoptotic pathways: ten minutes to dead. Cell, 2005, 121(5): 671-674

[21]

DenaultJ.B., BoatrightK.. Apoptosis in Biochemistry and Structural Biology. 3–8 February 2004, Keystone, CO, USA. IDrugs, 2004, 7(4): 315-317

[22]

VerrierF., DeniaudA., LebrasM., et al.. Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis. Oncogene, 2004, 23(49): 8049-8064

[23]

GreenD.R., ReedJ.C.. Mitochondria and apoptosis. Science, 1998, 281(5381): 1309-1312

[24]

DesagherS., MartinouJ.C.. Mitochondria as the central control point of apoptosis. Trends Cell Biol, 2000, 10(9): 369-377

[25]

LyJ.D., GrubbD.R., LawenA.. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis, 2003, 8(2): 115-128

[26]

WangX.. The expanding role of mitochondria in apoptosis. Genes Dev, 2001, 15(22): 2922-2933

[27]

KroemerG., ReedJ.C.. Mitochondrial control of cell death. Nat Med, 2000, 6(5): 513-519

[28]

ZamzamiN., MarchettiP., CastedoM., et al.. Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med, 1995, 181(5): 1661-1672

[29]

MoonD.O., ParkS.Y., ChoiY.H., et al.. Melittin induces Bcl-2 and caspase-3-dependent apoptosis through downregulation of Akt phosphorylation in human leukemic U937 cells. Toxicon, 2008, 51(1): 112-120

[30]

GrossA., McdonnellJ.M., KorsmeyerS.J.. BCL-2 family members and the mitochondria in apoptosis. Genes Dev, 1999, 13(15): 1899-1911

[31]

ZieglerD.S., KungA.L.. Therapeutic targeting of apoptosis pathways in cancer. Curr Opin Oncol, 2008, 20(1): 97-103

[32]

WajantH.. The Fas signaling pathway: more than a paradigm. Science, 2002, 296(5573): 1635-1636

[33]

MicheauO., SolaryE., HammannA., et al.. Fas ligand-independent, FADD-mediated activation of the Fas death pathway by anticancer drugs. J Biol Chem, 1999, 274(12): 7987-7992

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