Ferritin adsorption onto chrysotile asbestos fibers influences the protein secondary structure

Our plain-English summary of Ferritin adsorption onto chrysotile asbestos fibers influences the protein secondary structure, by M. Zangari, F. Piccirilli, L. Vaccari, et al (Heliyon, 2024).

The study

• Authors: M. Zangari, F. Piccirilli, L. Vaccari, C. Radu, P. Zacchi, A. Bernareggi, S. Leone, G. Zabucchi, V. Borelli
• Journal: Heliyon
• Published: 2024;10(20):e38966
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos fiber exposure triggers chronic inflammation and cancer. Asbestos fibers can adsorb different types of proteins. The mechanism of this adsorption, not yet completely understood, has been studied in detail mainly with serum albumin and was shown to induce structural changes in the bound protein. The findings of these works regarded mainly the changes of the protein structure, independently of any relation with asbestos-related diseases. For the first time, we have focused our attention to the consequences of the interaction between asbestos fibers and ferritin, a protein involved in iron metabolism, which is strongly modified in asbestos-related diseases. Even if it is known that ferritin can be adsorbed by asbestos fibers, the results of this interaction for the ferritin secondary structure has not previously been studied. One consequence of asbestos-ferritin interaction, is the formation of the so-called ferruginous/asbestos bodies (ABs). In the AB-coating material, the secondary structure of ferritin is modified, and at present, it is unclear whether or not this modification is a direct consequence of the asbestos interaction. In the present study, chrysotile asbestos, more than other asbestos fiber types tested, was found to rapidly bind holo-ferritin, and the presence of iron seemed to play a key role in this process, since iron-free apo-ferritin was adsorbed at a lower level, and iron-saturated chrysotile lost its ferritin-adsorbing capacity. To directly study the details of ferritin adsorption on asbestos fibers, High Resolution Transmission Electron Microscopy (HR-TEM) was employed together with FTIR microspectroscopy and Infrared nanoscopy, which to the best of our knowledge, have not previously been used for this purpose. Chrysotile-bound apo-ferritin underwent a significant change in secondary structure, showing a shift from a prevalent α-helix to a β-sheet conformation. Conversely, the adsorbed holo-ferritin structure appeared to be only weakly modified. These findings add a new potential mechanism to the toxic activities of asbestos: the fibers can modify the structure, and very likely, the function of adsorbed proteins. This, in relation to ferritin, could be a key mechanism in cell iron homeostasis alteration, typically reported in asbestos-related diseases.

© 2024 The Authors.

In plain English

This was a laboratory test-tube experiment, not a study of people. The authors mixed purified ferritin, an iron-storage protein taken from horse spleen, with standard samples of chrysotile, crocidolite and amosite asbestos. They used two forms of ferritin: iron-loaded holo-ferritin and iron-free apo-ferritin. Some conditions were meant to mimic the inside of cells.

Chrysotile bound more iron-loaded ferritin (0.108 plus or minus 0.018 micrograms of protein per microgram of fiber) than crocidolite (0.045) or amosite (0.021). Binding to chrysotile was fast, reaching about 80% of its maximum within 10 minutes. At pH 7.0, chrysotile bound significantly less iron-free ferritin than iron-loaded ferritin. At pH 5.0 the difference was not statistically significant. Chrysotile that had first been loaded with iron bound much less ferritin.

Infrared measurements showed that iron-loaded ferritin on chrysotile largely kept its normal shape. The iron-free form changed more severely, with part of the protein taking a beta-sheet form, which the authors interpreted as misfolding. The authors concluded that asbestos may have a new potential toxic activity, but stated that they did not prove the changes cause ferritin to lose its function.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment using purified proteins and asbestos fibers; no humans or animals were studied
• Who was studied: Purified iron-loaded ferritin (holo-ferritin) and iron-free ferritin (apo-ferritin) from horse spleen, combined with standard asbestos fiber samples
• Exposure: UICC standard asbestos samples: chrysotile (Rhodesian), crocidolite (South Africa) and amosite, 0.5 to 100 micrometers long and 0.1 to 1.2 micrometers wide. The fibers were incubated with ferritin at pH 5.0 and 7.0 in solutions mimicking the cell cytosol and phagosome, for times from minutes up to 1 week. Some chrysotile was first saturated with ferric iron.
• Main results:
  • Iron-loaded ferritin bound to chrysotile at 0.108 plus or minus 0.018 micrograms of protein per microgram of fiber (n = 10), compared with 0.045 for crocidolite (n = 3) and 0.021 for amosite (n = 3); the authors reported these differences as statistically significant
  • Binding of iron-loaded ferritin to chrysotile was fast: about 80% of the maximum after 10 minutes, with a plateau after 30 minutes
  • At pH 7.0, chrysotile bound significantly less iron-free ferritin than iron-loaded ferritin (P less than 0.01); at pH 5.0 the difference was not statistically significant
  • Chrysotile pre-saturated with iron showed strongly reduced binding of iron-loaded ferritin
  • Electron microscopy showed that ferritin often coated chrysotile unevenly, building up at specific sites on the fibers
  • Infrared nanoscopy suggested that iron-free ferritin sat mainly on the fiber surface, while iron-loaded ferritin was more intimately bound
  • The normal helix structure of iron-loaded ferritin bound to chrysotile was largely preserved under all tested conditions
  • Iron-free ferritin bound to chrysotile showed more severe structural rearrangement than iron-loaded ferritin, which the authors interpreted as misfolding, with part of the protein adopting a beta-sheet conformation
  • Iron-free ferritin left unbound in the liquid after incubation with chrysotile kept a spectrum like that of native iron-free ferritin
• The authors' conclusion: The authors concluded that asbestos fibers have a potential new toxic activity: they bind proteins and may change their function. They suggested that, for ferritin, this may very likely be one of the causal events leading to changes in iron balance, iron overload and lung inflammation.
• Limitations the authors state:
  • The authors did not prove that the misfolding causes loss of ferritin function or contributes to iron overload, and called this a limitation of the paper
  • Even with standard chrysotile, the authors could not be sure that the fiber amounts used had the same binding capacity
  • The authors did not investigate the chemical mechanism by which ferritin binds to chrysotile

Topics

Medical terms in this study, explained in our Lexicon: Ferritin, Chrysotile, Chronic Inflammation, Asbestos Bodies, Transmission Electron Microscopy (TEM).

Related studies

• Adsorption of bovine serum albumin onto synthetic Fe-doped geomimetic chrysotile — A. Adamiano, I.G. Lesci, et al. (2015)
• Adsorption isotherms of albumin and ferritin on Rhodesian chrysotile: effects of magnesium depletion — F. Valerio, M. Veggi, et al. (1980)
• Ferritin adsorption on amosite fibers: possible implications in the formation and toxicity of asbestos bodies — B. Fubini, F. Barceló, et al. (1997)
• Adsorption of proteins by chrysotile and crocidolite: role of molecular weight and charge density — F. Valerio, D. Balducci, et al. (1987)
• Selective adsorption of serum proteins by chrysotile and crocidolite — F. Valerio, D. Balducci, et al. (1986)
• Vitronectin adsorption to chrysotile asbestos increases fiber phagocytosis and toxicity for mesothelial cells — J. Wu, W. Liu, et al. (2000)

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