Distinct affinity of nuclear proteins to the surface of chrysotile and crocidolite

Abstract

The inhalation of asbestos is a risk factor for the development of malignant mesothelioma and lung cancer. Based on the broad surface area of asbestos fibers and their ability to enter the cytoplasm and nuclei of cells, it was hypothesized that proteins that adsorb onto the fiber surface play a role in the cytotoxicity and carcinogenesis of asbestos fibers. However, little is known about which proteins adsorb onto asbestos. Previously, we systematically identified asbestos-interacting proteins and classified them into eight sub-categories: chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton-associated proteins, histones and hemoglobin. Here, we report an adsorption profile of proteins for the three commercially used asbestos compounds: chrysotile, crocidolite and amosite. We quantified the amounts of adsorbed proteins by analyzing the silver-stained gels of sodium dodecyl sulfate-polyacrylamide gel electrophoresis with ImageJ software, using the bands for amosite as a standard. We found that histones were most adsorptive to crocidolite and that chromatin-binding proteins were most adsorptive to chrysotile. The results suggest that chrysotile and crocidolite directly interact with chromatin structure through different mechanisms. Furthermore, RNA-binding proteins preferably interacted with chrysotile, suggesting that chrysotile may interfere with transcription and translation. Our results provide novel evidence demonstrating that the specific molecular interactions leading to carcinogenesis are different between chrysotile and crocidolite.

Malignant mesothelioma as an oxidative stress-induced cancer: An update

“…Our laboratory demonstrated that the asbestos surface is able to adsorb more than 100 types of different proteins (including proteins such as histones and hemoglobin) as well as DNA and we provided evidence that the asbestos surface can serve as a niche that enhances oxidative modification. Our results revealed the presence of 4-hydroxy-2-nonenal modification and 8-OHdG, respectively, in the proteins and DNA adsorbed to the surface of asbestos fibers [37,60]. These studies all suggest that local excess iron is central to asbestos-induced carcinogenesis.…”

Bacterial Weathering of Asbestos

“…• "Adsorption theory" which tells that the positive or negative charges on the asbestos surface show high affinity for certain nuclear proteins particularly histones and chromatin binding proteins [5] leading to iron concentration in surrounding tissues.…”

Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

“…15,29,31 For adsorption, asbestos fibers (250 mg/ml) were incubated with membrane fraction proteins (1, 2, 5, 10, 20, 50, 100, 150, and 200 mg/ml) in PBS in a total volume of 1 ml at 37 1C while being shaken at 200 r.p.m. for 30 min.…”

“…25 The asbestos surface is well known to adsorb proteins. [27][28][29] Therefore, we hypothesized that asbestos fibers without a protein coating may bind to the receptor proteins on the mesothelial cell surface. To identify systematically the proteins involved in the mesothelial endocytosis of asbestos fibers, particularly candidate receptor proteins, we used an LTQ Orbitrap XL mass spectrometry system (Thermo Fisher Scientific, Waltham, MA, USA) combined with a Paradigm MS4 HPLC system (Michrom BioResources, Auburn, CA, USA), and evaluated the candidate proteins using shRNA (short hairpin RNA)-induced knockdown.…”