Iron mobilization from ferritin by chelating agents.
Abstract: The release of iron from horse spleen ferritin by the chelating agents desferrioxamine B, rhodotorulic acid, 2,3-dihydroxybenzoate, 2,2'-bipyridyl and pyridine-2-aldehyde-2-pyridyl hydrazone (Paphy) has been studied in vitro. Ferritin prepared by classical procedures involving thermal denaturation releases its iron less effectively than ferritin isolated by a modified procedure that avoids this step. Desferrioxamine B and rhodotorulic acid are the most effective in releasing iron from both preparations of ferritin. When FMN is added, iron release by desferrioxamine B, rhodotorulic acid, and 2,3-dihydroxybenzoate was effectively blocked, whereas both bipyridyl and Paphy showed a marked simulation. A substantial increase in iron release was also observed for bipyridyl and Paphy with ascorbate; a less important increase was noted for rhodotorulic acid. EDTA exerted a marked inhibition of iron release from ferritin with rhodotorulic acid, 2,3-dihydroxybenzoate, bipyridyl, and Paphy. The effects of citrate and oxalate on iron release by the chelators was small. The effect of the concentration of flavin on iron release from ferritin by bipyridyl and desferrioxamine B have been studied. Desferrioxamine is unable to mobilize FeII from ferritin following reduction by reduced FMN, whereas bipyridyl can rapidly complex the ferrous iron. The results are discussed in the context of our current concepts of storage iron mobilization in the treatment of iron overload.
Publication Date: 1980-12-01 PubMed ID: 7193239DOI: 10.1016/s0162-0134(00)80251-2Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates how different chelating agents can promote the release of iron from a protein called ferritin. The most efficient chelating agents were found to be desferrioxamine B and rhodotorulic acid, and other substances like FMN, ascorbate, and EDTA showed different levels of influence on the process.
Study Methodology
- The researchers studied the ability of various chelating agents – desferrioxamine B, rhodotorulic acid, 2,3-dihydroxybenzoate, 2,2′-bipyridyl and pyridine-2-aldehyde-2-pyridyl hydrazone (Paphy) – to release iron from ferritin prepared from horse spleen. They tested this using two different preparation methods for ferritin to comprehend any difference linked with its preparation.
Findings on Chelating Agents
- Desferrioxamine B and rhodotorulic acid were identified as the most effective agents to release iron from ferritin prepared in both ways. This implies these substances have a high binding efficiency with iron, allowing it to be mobilized from ferritin effectively.
- The other three agents – 2,3-dihydroxybenzoate, 2,2′-bipyridyl, and Paphy – had varying effectiveness. Particularly, when FMN (flavin mononucleotide) was added, the iron release with these three agents showed different results. For instance, iron release by 2,3-dihydroxybenzoate was blocked, while Paphy and bipyridyl resulted in boosted iron release.
Influence of Other Substances
- The inclusion of ascorbate significantly increased iron release in bipyridyl and Paphy. A smaller increase was seen with rhodotorulic acid.
- EDTA (Ethylenediaminetetraacetic acid) was found to inhibit iron release from ferritin when paired with rhodotorulic acid, 2,3-dihydroxybenzoate, bipyridyl, and Paphy. This suggests that EDTA may interfere with these chelating agents’ ability to mobilize iron from ferritin.
- The impacts of citrate and oxalate on iron release by the chelating agents were minimal, showing these substances don’t substantially impact the chelating abilities of examined agents.
Special Case of Flavin
- The researchers further investigated the effect of flavin concentration on the iron release by specific chelating agents – bipyridyl and desferrioxamine B. Interestingly, while bipyridyl was able to mobilize FeII from ferritin quickly after reduction by reduced FMN, desferrioxamine could not.
The findings of this study provide valuable insights into how different chelating agents and substances can influence iron mobilization from ferritin. It is beneficial in the broader context of understanding the treatment of conditions like iron overload.
Cite This Article
APA
Crichton RR, Roman F, Roland F.
(1980).
Iron mobilization from ferritin by chelating agents.
J Inorg Biochem, 13(4), 305-316.
https://doi.org/10.1016/s0162-0134(00)80251-2 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Chelating Agents
- Ferritins
- Horses
- Iron
- Kinetics
- Protein Binding
- Spleen
- Structure-Activity Relationship
Citations
This article has been cited 13 times.- Sha X, Chen H, Zhang J, Zhao G. Iron Release from Soybean Seed Ferritin Induced by Cinnamic Acid Derivatives.. Pharmaceuticals (Basel) 2018 May 4;11(2).
- Liu Z, Purro M, Qiao J, Xiong MP. Multifunctional Polymeric Micelles for Combining Chelation and Detection of Iron in Living Cells.. Adv Healthc Mater 2017 Sep;6(17).
- Segond D, Abi Khalil E, Buisson C, Daou N, Kallassy M, Lereclus D, Arosio P, Bou-Abdallah F, Nielsen Le Roux C. Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization.. PLoS Pathog 2014 Feb;10(2):e1003935.
- Theil EC, Chen H, Miranda C, Janser H, Elsenhans B, Núñez MT, Pizarro F, Schümann K. Absorption of iron from ferritin is independent of heme iron and ferrous salts in women and rat intestinal segments.. J Nutr 2012 Mar;142(3):478-83.
- Hasan MR, Tosha T, Theil EC. Ferritin contains less iron (59Fe) in cells when the protein pores are unfolded by mutation.. J Biol Chem 2008 Nov 14;283(46):31394-400.
- Porter JB. A risk-benefit assessment of iron-chelation therapy.. Drug Saf 1997 Dec;17(6):407-21.
- Hasinoff BB, Kala SV. The removal of metal ions from transferrin, ferritin and ceruloplasmin by the cardioprotective agent ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] and its hydrolysis product ADR-925.. Agents Actions 1993 May;39(1-2):72-81.
- Herman EH, Zhang J, Ferrans VJ. Comparison of the protective effects of desferrioxamine and ICRF-187 against doxorubicin-induced toxicity in spontaneously hypertensive rats.. Cancer Chemother Pharmacol 1994;35(2):93-100.
- Kontoghiorghes GJ. Iron mobilization from ferritin using alpha-oxohydroxy heteroaromatic chelators.. Biochem J 1986 Jan 1;233(1):299-302.
- Kontoghiorghes GJ, Chambers S, Hoffbrand AV. Comparative study of iron mobilization from haemosiderin, ferritin and iron(III) precipitates by chelators.. Biochem J 1987 Jan 1;241(1):87-92.
- Topham R, Goger M, Pearce K, Schultz P. The mobilization of ferritin iron by liver cytosol. A comparison of xanthine and NADH as reducing substrates.. Biochem J 1989 Jul 1;261(1):137-43.
- Haurani FI, Quinn TJ. Modulators of macrophage transferrin or transferrin-like protein.. Mol Cell Biochem 1990 Jun 1;95(1):49-53.
- al-Massad FK, Kadir FH, Moore GR. Animal ferritin and bacterioferritin contain quinones.. Biochem J 1992 Apr 1;283 ( Pt 1)(Pt 1):177-80.
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