Ward, Roberta J.
[UCL]
Kuhn, LC.
Kaldy, P.
Florence, A.
Peters, TJ.
Crichton, Robert
[UCL]
It has recently been proposed that cellular iron homeostasis in mammalian cells is regulated at the post-transcriptional level by the reciprocal control of transferrin receptor and ferritin mRNA expression via an iron-regulatory factor. This iron-regulatory factor has been shown to be a cytoplasmic aconitase which can bind to iron-responsive elements in the corresponding mRNAs with greater or lesser affinity as a function of the iron status of the cell. In the present study, we show that in vivo the affinity of iron-regulatory factor for iron-responsive elements in liver reflects the long-term iron status of the tissue in animal models for iron overloading and iron deficiency, when combined with altered transferrin saturation and serum iron levels. In contrast hepatic iron overload achieved without altering such haematopoeitic indices, had a less pronounced effect. In both spleen and heart, the affinities of iron-regulatory factor changed in parallel with both altered iron status and haematological markers. In brain and duodenum, there were no consistent changes in iron-regulatory-factor activity with iron loading or depletion. Iron-regulatory-factor activity in kidney responded in an as yet unexplained manner.
- Crichton R. R., Inorganic biochemistry of iron metabolism (1991)
- Klausner R. D., Science, 246, 870 (1989)
- Theil E. C., Adv. Enzymol. Relat. Areas Mol. Biol., 63, 421 (1990)
- Kuhn L. C., Br. Haematol., 79, 1 (1991)
- Kühn Lukas C., Hentze Matthias W., Coordmation of cellular iron metabolism by post-transcriptional gene regulation, 10.1016/0162-0134(92)84064-t
- Klausner Richard D., Rouault Tracey A., Harford Joe B., Regulating the fate of mRNA: The control of cellular iron metabolism, 10.1016/0092-8674(93)90046-s
- Aziz N., Proc. Natl Acad. Sci. USA, 84, 2277 (1987)
- Hentze M. W., Science, 238, 1570 (1987)
- Cox T. C., EMBO J., 10, 1891 (1991)
- Dandekar T., EMBO J., 10, 1903 (1991)
- Casey J. L., Science, 240, 924 (1988)
- Müllner Ernst W., Neupert Barbara, Kühn Lukas C., A specific mRNA binding factor regulates the iron-dependent stability of cytoplasmic transferrin receptor mRNA, 10.1016/0092-8674(89)90851-9
- Chan L. N., Nucleic Acids Res., 17, 3763 (1989)
- Roberts K. P., Mol. Endocrinol., 4, 531 (1990)
- Hentze M. W., Science, 244, 357 (1989)
- Walden W. E., J. Biol. Chem., 264, 13765 (1989)
- Leibold E. A., Proc. Natl Acad. Sci. USA, 85, 2171 (1988)
- Rouault T. A., Science, 241, 1207 (1988)
- Koeller D. M., Proc. Natl Acad. Sci. USA, 86, 3574 (1989)
- Müllner Ernst W., Kühn Lukas C., A stem-loop in the 3′ untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm, 10.1016/0092-8674(88)90098-0
- Kennedy M. C., Proc Natl Acad. Sci. USA, 89, 11730 (1992)
- Haile D. J., Proc. Natl Acad. Sci. USA, 89, 11730 (1992)
- Emery-Goodman A., Nucleic Acids Res., 21, 1457 (1993)
- Ward R. J., Eur. J. Biochem., 202, 405 (1991)
- Mullner E. W., Eur. J. Biochem., 208, 597 (1992)
- Barton H. A., J. Biol. Chem., 265, 7000 (1990)
- Saito K., Br. J. Haematol., 62, 275 (1986)
- Kondo H., Hepatology, 8, 32 (1988)
- Mack U., J. Biol. Chem., 258, 4672 (1983)
- Sibille J.-C., Hepatology, 8, 296 (1988)
- Nielson P., Biochem. Pharmacol., 44, 322 (1992)
- Testa U., J. Biol. Chem., 266, 13925 (1991)
- Teixeira S., Eur. J. Biochem., 202, 819 (1991)
- Seisar C., J. Biol. Chem., 268, 13074 (1993)
- Mack U., Br. J. Haematol., 47, 403 (1981)
Bibliographic reference |
Ward, Roberta J. ; Kuhn, LC. ; Kaldy, P. ; Florence, A. ; Peters, TJ. ; et. al. Control of Cellular Iron Homeostasis By Iron-responsive Elements In-vivo. In: European Journal of Biochemistry, Vol. 220, no. 3, p. 927-931 (1994) |
Permanent URL |
http://hdl.handle.net/2078.1/49051 |