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Regulation and trafficking of the iron export protein, ferroportin1, in Mycobacterium tuberculosis-infected macrophages

Van Zandt, Kristopher Edward
http://rave.ohiolink.edu/etdc/view?acc_num=osu1189541356

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Microbiology.
Intracellular pathogens, including Mycobacterium tuberculosis, obtain iron required for survival from the host. Ferroportin1 (SLC40a1, FPN1) is the sole exporter of iron from mammalian cells and is expressed in the duodenum and macrophages. In the present study, we show that FPN1 mRNA levels in the mouse macrophage cell line RAW264.7 are synergistically induced by treatment with M. tuberculosis and IFN-gamma. Similar results were obtained using live M. tuberculosis and gamma-irradiated M. tuberculosis. FPN1 mRNA levels were also increased by M. avium and IFN-gamma in RAW264.7 cells and mouse alveolar macrophage cell line AMJ2-C8. Treatment of mouse resident peritoneal macrophages with M. tuberculosis and IFN-gamma resulted in a 6-fold increase in FPN1 mRNA expression. In contrast, M. tuberculosis and IFN-gamma inhibited FPN1 mRNA expression in bone marrow derived macrophages (BMDMs). Using confocal microscopy, FPN1 protein rapidly localized to M. tuberculosis-containing phagosomes after infection, while FPN1 did not localize to latex bead-containing phagosomes. Our studies suggest that macrophage FPN1 expression is regulated at the level of mRNA expression, protein expression, and trafficking. The presence of this iron export protein in M. tuberculosis phagosome suggests that it is involved in limiting iron availability to the invading mycobacteria. We also examined the promoter activity of the ferroportin1 gene. Using a clone of this region, we found that there are four nuclear transcription factor binding sites; one for PU.1, one for STAT1, and two for NFêB. We found that all four sites are important for expression of ferroportin1, as a loss of any of them results in a complete loss of ferroportin1 promoter activity. We also found that iron levels do not affect promoter activity, indicating that ferroportin1 expression is regulated by iron levels primarily post-transcriptionally.
Abhay Satoskar (Advisor)
137 p.
Biology, Microbiology
iron; ferroportin1; Mycobacterium tuberculosis; Nramp1

Recommended Citations

Citations

  • Van Zandt, K. E. (2007). Regulation and trafficking of the iron export protein, ferroportin1, in Mycobacterium tuberculosis-infected macrophages [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1189541356

    APA Style (7th edition)

  • Van Zandt, Kristopher. Regulation and trafficking of the iron export protein, ferroportin1, in Mycobacterium tuberculosis-infected macrophages. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1189541356.

    MLA Style (8th edition)

  • Van Zandt, Kristopher. "Regulation and trafficking of the iron export protein, ferroportin1, in Mycobacterium tuberculosis-infected macrophages." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1189541356

    Chicago Manual of Style (17th edition)

osu1189541356
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© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.