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Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis.

Wang Y, Okazaki Y, Shi L, Kohda H, Tanaka M, Taki K, Nishioka T, Hirayama T, Nagasawa H, Yamashita Y, Toyokuni S - Cancer Sci. (2016)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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Related in: MedlinePlus

Transferrin receptor 1 plays a role in the uptake of NT50 by rat peritoneal mesothelial cells. Difference in the uptake of NT50 by rat peritoneal mesothelial cells with ([b] Lys‐NT50) or without ([a] Nt‐NT50) protein coating (a). The number of cells which internalized or attached Nt‐NT50 or Tf‐NT50 was measured by flow cytometer (b). Ferristatin II reduced the levels of transferrin receptor 1 (arrow) (c), which induced decreased uptake of Tf‐NT50 (d). Whereas ferristatin II treatment alone did not change the level of cytoplasmic catalytic Fe(II), ferristatin II treatment significantly decreased the amounts of catalytic Fe(II) upon exposure to Tf‐NT50 (N = 3, means ± SEM). Please refer to the text and Figure 4 for details. CNT, carbon nanotubes.
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cas12865-fig-0006: Transferrin receptor 1 plays a role in the uptake of NT50 by rat peritoneal mesothelial cells. Difference in the uptake of NT50 by rat peritoneal mesothelial cells with ([b] Lys‐NT50) or without ([a] Nt‐NT50) protein coating (a). The number of cells which internalized or attached Nt‐NT50 or Tf‐NT50 was measured by flow cytometer (b). Ferristatin II reduced the levels of transferrin receptor 1 (arrow) (c), which induced decreased uptake of Tf‐NT50 (d). Whereas ferristatin II treatment alone did not change the level of cytoplasmic catalytic Fe(II), ferristatin II treatment significantly decreased the amounts of catalytic Fe(II) upon exposure to Tf‐NT50 (N = 3, means ± SEM). Please refer to the text and Figure 4 for details. CNT, carbon nanotubes.

Mentions: After treating RPMC with Nt‐NT50 or Lys‐NT50, we observed a difference in uptake, suggesting that an interaction between nanotube surface protein and its receptor may promote NT50 internalization (Fig. 6a). To evaluate whether NT50 uptake was associated with the plasma membrane receptor for Tf, flow cytometric analysis was performed33 to calculate the number of cells revealing NT50 uptake by counting 10 000 cells. Tf‐NT50 induced approximately 20% more uptake of CNT by RPMC than Nt‐NT50 (Fig. 6b). TfR1 (TFRC, CD71) is the main receptor of transferrin. Ferristatin II is a specific inhibitor of TfR1, and the ferristatin II‐induced decrease in TfR1 protein levels was confirmed with western blot analysis (Fig. 6c). Ferristatin II significantly decreased the amount of Tf‐NT50 penetrating the cells (Fig. 6d). Simultaneously, the level of catalytic ferrous iron was also decreased in Tf‐NT50‐treated cells after ferristatin II addition (Fig. 6e).


Role of hemoglobin and transferrin in multi-wall carbon nanotube-induced mesothelial injury and carcinogenesis.

Wang Y, Okazaki Y, Shi L, Kohda H, Tanaka M, Taki K, Nishioka T, Hirayama T, Nagasawa H, Yamashita Y, Toyokuni S - Cancer Sci. (2016)

Transferrin receptor 1 plays a role in the uptake of NT50 by rat peritoneal mesothelial cells. Difference in the uptake of NT50 by rat peritoneal mesothelial cells with ([b] Lys‐NT50) or without ([a] Nt‐NT50) protein coating (a). The number of cells which internalized or attached Nt‐NT50 or Tf‐NT50 was measured by flow cytometer (b). Ferristatin II reduced the levels of transferrin receptor 1 (arrow) (c), which induced decreased uptake of Tf‐NT50 (d). Whereas ferristatin II treatment alone did not change the level of cytoplasmic catalytic Fe(II), ferristatin II treatment significantly decreased the amounts of catalytic Fe(II) upon exposure to Tf‐NT50 (N = 3, means ± SEM). Please refer to the text and Figure 4 for details. CNT, carbon nanotubes.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814253&req=5

cas12865-fig-0006: Transferrin receptor 1 plays a role in the uptake of NT50 by rat peritoneal mesothelial cells. Difference in the uptake of NT50 by rat peritoneal mesothelial cells with ([b] Lys‐NT50) or without ([a] Nt‐NT50) protein coating (a). The number of cells which internalized or attached Nt‐NT50 or Tf‐NT50 was measured by flow cytometer (b). Ferristatin II reduced the levels of transferrin receptor 1 (arrow) (c), which induced decreased uptake of Tf‐NT50 (d). Whereas ferristatin II treatment alone did not change the level of cytoplasmic catalytic Fe(II), ferristatin II treatment significantly decreased the amounts of catalytic Fe(II) upon exposure to Tf‐NT50 (N = 3, means ± SEM). Please refer to the text and Figure 4 for details. CNT, carbon nanotubes.
Mentions: After treating RPMC with Nt‐NT50 or Lys‐NT50, we observed a difference in uptake, suggesting that an interaction between nanotube surface protein and its receptor may promote NT50 internalization (Fig. 6a). To evaluate whether NT50 uptake was associated with the plasma membrane receptor for Tf, flow cytometric analysis was performed33 to calculate the number of cells revealing NT50 uptake by counting 10 000 cells. Tf‐NT50 induced approximately 20% more uptake of CNT by RPMC than Nt‐NT50 (Fig. 6b). TfR1 (TFRC, CD71) is the main receptor of transferrin. Ferristatin II is a specific inhibitor of TfR1, and the ferristatin II‐induced decrease in TfR1 protein levels was confirmed with western blot analysis (Fig. 6c). Ferristatin II significantly decreased the amount of Tf‐NT50 penetrating the cells (Fig. 6d). Simultaneously, the level of catalytic ferrous iron was also decreased in Tf‐NT50‐treated cells after ferristatin II addition (Fig. 6e).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Show MeSH
Related in: MedlinePlus