TAILIEUCHUNG - Báo cáo Y học: Complexation of ytterbium to human transferrin and its uptake by K562 cells

There is an increasing interest in the use of lanthanides in medicine. However, themechanismof their accumulation in cells isnotwell are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptormediated transport is possible; however, this has not yet been confirmed. In order to clarify this mechanism, we investigated the binding of Yb 3+ to apo-transferrin by UV-Vis spectroscopy and stopped-flow spec-trophotometry, and found that Yb 3+ binds to apotransferrin at the specific iron sites in the presence of bicarbonate. . | Eur. J. Biochem. 269 6082-6090 2002 FEBS 2002 doi Complexation of ytterbium to human transferrin and its uptake by K562 cells Xiu-lian Du1. Tian-lan Zhang1. Lan Yuan1 Yong-vuan Zhao1 Rong-chang Li1 Kui Wang1 Siu Cheong Yan2. Li Zhang2 Hongzhe Sun2 and Zhong-ming Qian3 1Department of Chemical Biology School of Pharmaceutical Sciences Peking University Beijing China department of Chemistry and Open Laboratory of Chemical Biology University of Hong Kong Hong Kong 3Department of Applied Biology and Chemical Technology Hong Kong Polytechnic University Kowloon Hong Kong There is an increasing interest in the use of lanthanides in medicine. However the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding suggesting transferrin-receptor mediated transport is possible however this has not yet been confirmed. In order to clarify this mechanism we investigated the binding of Yb3 to apotransferrin by UV-Vis spectroscopy and stopped-flow spectrophotometry and found that Yb3 binds to apotransferrin at the specific iron sites in the presence of bicarbonate. The apparent binding constants of these sites showed that the affinity of Yb3 is lower than that of Fe3 and binding of Yb3 in the N-lobe is kinetically favored while the C-lobe is thermodynamically favored. The first Yb3 bound to the C-lobe quantitatively with a Yb apotransferrin molar ratio of 1 whereas the binding to the other site is weaker and approaches completeness by a higher molar ratio only. As demonstrated by 1H NMR spectra Yb3 binding disturbed the conformation of apotransferrin in a manner similar to Fe3 . Flow cytometric studies on the uptake of fluorescein isothiocyanate labeled Yb3 -bound transferrin species by K562 cells showed that they bind to the cell receptors. Laser scanning confocal microscopic studies with fluorescein isothiocyanate labeled Yb3 -bound transferrin and propidium .

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