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ROS-induced ZNF580 expression: a key role for H2O2/NF-κB signaling pathway in vascular endothelial inflammation

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Abstract

ZNF580, a newly found C2H2 zinc finger transcription factor, was first described by Zhang (GenBank ID: AF184939). Emerging evidence has suggested that reactive oxygen species (ROS) play an important role in redox-sensitive signal transduction, and the vascular endothelium plays a critical role in the vascular inflammatory response. In this communication, we present evidence for the potential role of ZNF580 in hydrogen peroxide (H2O2)-regulated inflammation-related signaling pathways. In a human endothelial cell hybridoma line (EA.hy926), ZNF580 levels were markedly upregulated with H2O2 stimulation in different concentrations (0–400 μM) and at different time-points (0–6 h). H2O2 promoted the rapid translocation of p65 from the cytoplasm into the nucleus according to immunocytochemistry staining. In subsequent research, inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB) was shown to block the upregulated expression of ZNF580 that was induced by H2O2. Furthermore, transient transfection of ZNF580 resulted in an increase of the pro-inflammatory cytokine interleukin-8 (IL-8) 3.01 ± 0.05 folds according to real-time RT-PCR and ELISA assays, which also showed significantly enhanced motility of human acute monocytic leukemia cells (THP-1). These results suggest that H2O2 upregulates the expression of ZNF580 via the NF-κB signaling pathway, and overexpression of ZNF580 plays a critical role in augmenting the release of pro-inflammatory cytokine IL-8.

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References

  1. Zhang W, Chen B, Zeng W, Wu G, Xue H (2003) Cloning and tissue expression of a novel gene down-regulated by low density lipoprotein. Basic Med Sci Clin 23:279–282

    Google Scholar 

  2. Zhang W, Chen B, Zeng W, Wu G, Xue H (2001) Cloning and structural analysis of a novel gene down-regulated by low density lipoprotein. Nat Med J China 81:435–436

    CAS  Google Scholar 

  3. Chanchevalap S, Nandan MO, McConnell BB, Charrier L, Merlin D, Katz JP, Yang VW (2006) Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells. Nucleic Acids Res 34:1216–1223

    Article  PubMed  CAS  Google Scholar 

  4. Cooper JT, Stroka DM, Brostjan C, Palmetshofer A, Bach FH, Ferran C (1996) A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. J Biol Chem 271:18068–18073

    Article  PubMed  CAS  Google Scholar 

  5. Liang J, Wang J, Azfer A, Song W, Tromp G, Kolattukudy PE, Fu M (2008) A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages. J Biol Chem 283:6337–6346

    Article  PubMed  CAS  Google Scholar 

  6. Zhang W, Sun H, Luo Y, Cui M (2008) Construction of eukaryotic expression vector for ZNF580 and EGFP fusion protein and its expression and localization in HEK293 cells. Acta Acad Med CAPF 17:161–165

    CAS  Google Scholar 

  7. Zhang W, Sun H, Meng X (2008) Subcellular localization of ZNF580-EGFP fusion protein. Chin J Pathophysiol 24:1590–1594

    CAS  Google Scholar 

  8. Sun HY, Wei SP, Xu RC, Xu PX, Zhang WC (2010) Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: novel insights into angiogenesis. Biochem Biophys Res Commun 395:361–366

    Google Scholar 

  9. Hoffmanna CJ, Hohberg M, Chlench S, Maroski J, Drab M, Siegel G, Pries AR, Zakrzewicz A (2011) Suppression of zinc finger protein 580 by high oxLDL/LDL-ratios is followed by enhanced expression of endothelial IL-8. Atherosclerosis 216(1):103–108

    Google Scholar 

  10. Groeger G, Quiney C, Cotter TG (2009) Hydrogen peroxide as a cell-survival signaling molecule. Antioxid Redox Signal 11:2655–2671

    Article  PubMed  CAS  Google Scholar 

  11. Frey RS, Ushio-Fukai M, Malik AB (2009) NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. Antioxid Redox Signal 11:791–810

    Article  PubMed  CAS  Google Scholar 

  12. True AL, Rahman A, Malik AB (2000) Activation of NF-κB induced by H2O2 and TNF-αand its effects on ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol 279:L302–L311

    Google Scholar 

  13. Liu J, Yoshida Y, Yamashita U (2007) Suppressive effect of reactive oxygen species on CD40-induced B cell activation. FEBS Lett 581:5043–5049

    Article  PubMed  CAS  Google Scholar 

  14. Kroncke KD (2003) Nitrosative stress and transcription. Biol Chem 384:1365–1377

    Article  PubMed  Google Scholar 

  15. Enesa K, Ito K, Luong le A, Thorbjornsen I, Phua C, To Y, Dean J, Haskard DO, Boyle J, Adcock I, Evans PC (2008) Hydrogen peroxide prolongs nuclear localization of NF-kappaB in activated cells by suppressing negative regulatory mechanisms. J Biol Chem 283:18582–18590

    Article  PubMed  CAS  Google Scholar 

  16. Jin XH, Ohgami K, Shiratori K, Koyama Y, Yoshida K, Kase S, Ohno S (2007) Inhibition of nuclear factor-kappa B activation attenuates hydrogen peroxide-induced cytotoxicity in human lens epithelial cells. Br J Ophthalmol 91:369–371

    Article  PubMed  Google Scholar 

  17. Lakshminarayanan V, Beno DW, Costa RH, Roebuck KA (1997) Differential regulation of interleukin-8 and intercellular adhesion molecule-1 by H2O2 and tumor necrosis factor-alpha in endothelial and epithelial cells. J Biol Chem 272:32910–32918

    Article  PubMed  CAS  Google Scholar 

  18. Hamik A, Lin Z, Kumar A, Balcells M, Sinha S, Katz J, Feinberg MW, Gerzsten RE, Edelman ER, Jain MK (2007) Kruppel-like factor 4 regulates endothelial inflammation. J Biol Chem 282:13769–13779

    Article  PubMed  CAS  Google Scholar 

  19. Gustin C, Van Steenbrugge M, Raes M (2008) LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells. Am J Physiol Cell Physiol 295:C905–C914

    Article  PubMed  CAS  Google Scholar 

  20. Stone JR, Yang S (2006) Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal 8:243–270

    Article  PubMed  CAS  Google Scholar 

  21. Oliveira-Marques V, Marinho HS, Cyrne L, Antunes F (2009) Role of hydrogen peroxide in NF-kappaB activation: from inducer to modulator. Antioxid Redox Signal 11:2223–2243

    Article  PubMed  CAS  Google Scholar 

  22. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84

    Article  PubMed  CAS  Google Scholar 

  23. Yasuda M, Ohzeki Y, Shimizu S, Naito S, Ohtsuru A, Yamamoto T, Kuroiwa Y (1999) Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 in endothelial cells. Life Sci 64:249–258

    Article  PubMed  CAS  Google Scholar 

  24. Shono T, Ono M, Izumi H, Jimi SI, Matsushima K, Okamoto T, Kohno K, Kuwano M (1996) Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol Cell Biol 16:4231–4239

    PubMed  CAS  Google Scholar 

  25. Hafizah AH, Zaiton Z, Zulkhairi A, Mohd Ilham A, Nor Anita MM, Zaleha AM (2010) Piper sarmentosum as an antioxidant on oxidative stress in human umbilical vein endothelial cells induced by hydrogen peroxide. J Zhejiang Univ Sci B 11:357–365

    Google Scholar 

  26. Djordjevica T, Pogrebniaka A, BelAibaa RS, Bonelloa S, Wotzlawb C, Ackerb H, Hessa J, Gfrlacha A (2005) The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells. Free Radic Biol Med 38:616–630

    Article  Google Scholar 

  27. Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25:29–38

    Article  PubMed  CAS  Google Scholar 

  28. Zhou Z, Gengaro P, Wang W, Wang XQ, Li C, Faubel S, Rivard C, Schrier RW (2008) Role of NF-kappaB and PI 3-kinase/Akt in TNF-alpha-induced cytotoxicity in microvascular endothelial cells. Am J Physiol Renal Physiol 295:F932–F941

    Article  PubMed  CAS  Google Scholar 

  29. Munoz C, Pascual-Salcedo D, Castellanos MC, Alfranca A, Aragones J, Vara A, Redondo JM, de Landazuri MO (1996) Pyrrolidine dithiocarbamate inhibits the production of interleukin-6, interleukin-8, and granulocyte-macrophage colony-stimulating factor by human endothelial cells in response to inflammatory mediators: modulation of NF-kappa B and AP-1 transcription factors activity. Blood 88:3482–3490

    PubMed  CAS  Google Scholar 

  30. Yoshida A, Yoshida S, Ishibashi T, Kuwano M, Inomata H (1999) Suppression of retinal neovascularization by the NF-kappaB inhibitor pyrrolidine dithiocarbamate in mice. Invest Ophthalmol Vis Sci 40:1624–1629

    PubMed  CAS  Google Scholar 

  31. Ebenezer PJ, Mariappan N, Elks CM, Haque M, Soltani Z, Reisin E, Francis J (2009) Effects of pyrrolidine dithiocarbamate on high-fat diet-induced metabolic and renal alterations in rats. Life Sci 85:357–364

    Article  PubMed  CAS  Google Scholar 

  32. Hu CJ, Lee YL, Shih NY, Yang YY, Charoenfuprasert S, Dai YS, Chang SM, Tsai YH, Tseng H, Liu CY, Leu SJ (2009) Reduction of monocyte chemoattractant protein-1 and interleukin-8 levels by ticlopidine in TNF-alpha stimulated human umbilical vein endothelial cells. J Biomed Biotechnol 2009:917837

  33. Maldonado-Perez D, Brown P, Morgan K, Millar RP, Thompson EA, Jabbour HN (2009) Prokineticin 1 modulates IL-8 expression via the calcineurin/NFAT signaling pathway. Biochim Biophys Acta 1793:1315–1324

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to our colleagues in the Department of Physiology and Pathophysiology, Medical College of the Chinese People’s Armed Police Force (CAPF), for their excellent technical assistance and encouragement. This project was supported by grants from the Chinese National Natural Science Foundation (No. 30770885) and Tianjin Natural Science Foundation (No. 10JCYBJC26500) and the Science Foundation of CPAF Medical College (No. WYZ2007-2).

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No competing financial interests exist.

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Authors and Affiliations

  1. Department of Clinical Laboratory, The Affiliated Hospital Medical College of Chinese People’s Armed Police Force, Tianjin, 300162, China

    Ren DangLi, Wang HeKong, Liu JiQin & Zhang MingHua

  2. Department of Physiology and Pathophysiology, Medical College of Chinese People’s Armed Police Force, Tianjin, 300162, China

    Zhang WenCheng

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  1. Ren DangLi
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  2. Wang HeKong
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  3. Liu JiQin
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  4. Zhang MingHua
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Correspondence to Zhang WenCheng.

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Ren DangLi and Wang HeKong contributed equally to this work.

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DangLi, R., HeKong, W., JiQin, L. et al. ROS-induced ZNF580 expression: a key role for H2O2/NF-κB signaling pathway in vascular endothelial inflammation. Mol Cell Biochem 359, 183–191 (2012). https://doi.org/10.1007/s11010-011-1013-0

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  • DOI: https://doi.org/10.1007/s11010-011-1013-0

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