Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis.
Bottom Line: Knockdown of transferrin receptor with ferristatin II decreased not only NT50 uptake but also cellular catalytic ferrous iron.Our results suggest that adsorption of hemoglobin and transferrin on the surface of NT50 play a role in causing mesothelial iron overload, contributing to oxidative damage and possibly subsequent carcinogenesis in mesothelial cells.Modifications of NT50 surface may decrease this human risk.
Affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.Show MeSH
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Mentions: To exhaustively identify proteins adsorbed on MWCNT, we undertook both in‐solution and in‐gel digestion methods. With the in‐solution digestion method, we identified 321 proteins from NT50, 131 proteins from NT100, 231 proteins from NT150 and 287 proteins from NTtngl (Tables 1 and S2). The results of the in‐solution digestion method revealed that NT50 and NTtngl shared the highest number of proteins among the four MWCNT (Fig. 2a). More than 400 proteins were identified and classified (Table S2). These included histones and many proteins associated with iron metabolism or oxidative stress. We picked up histones 2A/2B/3, hemoglobin α chain, hemoglobin β chain, Keap1, transferrin and peroxiredoxin 6 for confirmation (Fig. 2b). For histones, each of the four CNT fiber types revealed similar affinities (Fig. 2b[i]). However, for the other proteins studied, NT50 and NTtngl adsorbed significantly larger amounts of the proteins investigated than did NT100, NT150 or crocidolite, with similar affinities, except for transferrin (Fig. 2b[ii]). Generally, the results were proportional to the surface area of each CNT (Fig. S1). NT50, which is potently carcinogenic to mesothelial cells, showed a higher affinity for transferrin than NTtngl, which shows no carcinogenicity to mesothelial cells.18
Affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.