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PMID: 19688112 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Chlamydia trachomatis alters iron-regulatory protein-1 binding capacity and modulates cellular iron homeostasis in HeLa-229 cells.

Journal of biomedicine & biotechnology ·Vol. 2009 ·2009-00-00 ·Pages 342032

Vardhan H, Bhengraj AR, Jha R, Singh Mittal A

Abstract

Chlamydia trachomatis (CT) is the leading cause of diseases related to reproductive health and iron plays important role in chlamydial pathogenesis. Iron homeostasis in chlamydia-infected cells is not clear thus far. This study shows that expression of the transferrin receptor (TfR) is downregulated, whereas expression of the ferritin heavy chain is upregulated in CT-infected HeLa-229 cells. Expression of iron-regulatory protein (IRP)-1 predominates over IRP-2 in infected cells. In infected cells, attenuated binding activity of IRP-iron responsive elements (IREs) is observed using the electrophoretic mobility-shift assay. These results suggest that iron homeostasis is modulated in CT-infected HeLa cells at the interface of acquisition and commensal use of iron.

MeSH Terms
Analysis of Variance Apoferritins/biosynthesis,genetics,metabolism Chlamydia Infections/genetics,metabolism Chlamydia trachomatis/metabolism Down-Regulation HeLa Cells Humans Iron/metabolism Iron Regulatory Protein 1/biosynthesis,genetics,metabolism Iron Regulatory Protein 2/biosynthesis,genetics,metabolism Protein Binding Receptors, Transferrin/biosynthesis,genetics,metabolism Response Elements Up-Regulation
Chemicals
Receptors, Transferrin Apoferritins Iron Iron Regulatory Protein 1 Iron Regulatory Protein 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vardhan Harsh
Division of Microbiology/Tissue Culture, Institute of Pathology, Indian Council of Medical Research (ICMR), Safdarjung Hospital Campus, New Delhi, Pin 110029, India.
Bhengraj Apurb R
Jha Rajneesh
Singh Mittal Aruna
References (30)
30 references, click to expand
  1. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis.
    Microbiol Rev. 1994 Dec;58(4):686-99 PMID: 7854252
  2. Identification of Chlamydia trachomatis genomic sequences recognized by chlamydial divalent cation-dependent regulator A (DcrA).
    J Bacteriol. 2005 Jan;187(2):443-8 PMID: 15629915
  3. Balancing acts: molecular control of mammalian iron metabolism.
    Cell. 2004 Apr 30;117(3):285-97 PMID: 15109490
  4. Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15971-6 PMID: 14673075
  5. Iron metabolism and the IRE/IRP regulatory system: an update.
    Ann N Y Acad Sci. 2004 Mar;1012:1-13 PMID: 15105251
  6. Leishmania donovani depletes labile iron pool to exploit iron uptake capacity of macrophage for its intracellular growth.
    Cell Microbiol. 2009 Jan;11(1):83-94 PMID: 18823384
  7. Chlamydial persistence: beyond the biphasic paradigm.
    Infect Immun. 2004 Apr;72(4):1843-55 PMID: 15039303
  8. Low-nutrient induction of abnormal chlamydial development: a novel component of chlamydial pathogenesis?
    FEMS Microbiol Lett. 1993 Jan 15;106(2):193-200 PMID: 8454184
  9. The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3569-74 PMID: 12655056
  10. The role of iron regulatory proteins in mammalian iron homeostasis and disease.
    Nat Chem Biol. 2006 Aug;2(8):406-14 PMID: 16850017
  11. Novel roles for iron regulatory proteins in the adaptive response to iron deficiency.
    J Nutr. 2003 May;133(5 Suppl 1):1510S-6S PMID: 12730455
  12. Cytokine-mediated regulation of iron transport in human monocytic cells.
    Blood. 2003 May 15;101(10):4148-54 PMID: 12522003
  13. A model for the structure and functions of iron-responsive elements.
    Gene. 1988 Dec 10;72(1-2):201-8 PMID: 3266604
  14. Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence.
    Infect Immun. 1994 Sep;62(9):3705-11 PMID: 8063385
  15. A phosphomimetic mutation at Ser-138 renders iron regulatory protein 1 sensitive to iron-dependent degradation.
    Mol Cell Biol. 2003 Oct;23(19):6973-81 PMID: 12972614
  16. Transcriptional profile of Toxoplasma gondii-infected human fibroblasts as revealed by gene-array hybridization.
    Mol Genet Genomics. 2001 Jul;265(5):905-12 PMID: 11523808
  17. Induction of alpha/beta interferon and dependent nitric oxide synthesis during Chlamydia trachomatis infection of McCoy cells in the absence of exogenous cytokine.
    Infect Immun. 1996 Oct;64(10):3951-6 PMID: 8926054
  18. Ultrastructural analysis of the effects of erythromycin on the morphology and developmental cycle of Chlamydia trachomatis HAR-13.
    Arch Microbiol. 1982 Dec 3;133(4):278-82 PMID: 7171287
  19. Iron regulatory protein 2 as iron sensor. Iron-dependent oxidative modification of cysteine.
    J Biol Chem. 2003 Apr 25;278(17):14857-64 PMID: 12591920
  20. Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting intracellular iron.
    Infect Immun. 1991 Dec;59(12):4684-6 PMID: 1937829
  21. Regulation of ferritin genes and protein.
    Blood. 2002 May 15;99(10):3505-16 PMID: 11986201
  22. Cultivation and Laboratory Maintenance of Chlamydia trachomatis.
    Curr Protoc Microbiol. 2005 Jul;Chapter 11:Unit 11A.1 PMID: 18770550
  23. Converse modulation of IRP1 and IRP2 by immunological stimuli in murine RAW 264.7 macrophages.
    J Biol Chem. 1998 Apr 17;273(16):9403-8 PMID: 9545264
  24. Response of Chlamydia trachomatis serovar E to iron restriction in vitro and evidence for iron-regulated chlamydial proteins.
    Infect Immun. 1997 Nov;65(11):4539-47 PMID: 9353031
  25. Activation of iron regulatory protein-1 by oxidative stress in vitro.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10559-63 PMID: 9724742
  26. Novel role of phosphorylation in Fe-S cluster stability revealed by phosphomimetic mutations at Ser-138 of iron regulatory protein 1.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15235-40 PMID: 9860952
  27. Examination of an inducible expression system for limiting iron availability during Chlamydia trachomatis infection.
    Microbes Infect. 2007 Jul;9(8):947-53 PMID: 17544798
  28. Interaction of chlamydiae and host cells in vitro.
    Microbiol Rev. 1991 Mar;55(1):143-90 PMID: 2030670
  29. Etiology and outcome of acute pelvic inflammatory disease.
    J Infect Dis. 1988 Sep;158(3):510-7 PMID: 3045213
  30. Origins and functions of the chlamydial inclusion.
    Trends Microbiol. 1997 Jul;5(7):288-93 PMID: 9234512
Article Info
Journal
Journal of biomedicine & biotechnology
Abbr.
J Biomed Biotechnol
ISSN
1110-7251
Published
2009-00-00
Epub
2009-00-16
Pages
342032
Language
English
Region
United States
NLM ID
101135740
PMCID
PMC2727623
Subset
IM
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