ToxSci Advance Access published online on January 21, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh024
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University; Kennedy-Krieger Institute, Baltimore, MD, 21205; School of Pharmacy, Sahmyook University, Seoul, Korea
* To whom correspondence should be addressed. E-mail: Bressler{at}kennedykrieger.org.
The mechanism by which lead (Pb) enters astrocytes was examined in a rat astroglial cell line in order to characterize specific pathways for transport. Pb uptake was saturable at pH 5.5 and 7.4, although quantitative differences existed in the Michaelis-Menten constants. At pH 7.4, the Vmax and Km was 2700 fmoles/mg protein/min and 13.4 µM, respectively, whereas the Vmax and Km was 329 fmoles/mg and 8.2 µM in the buffer at pH 5.5, respectively. The presence of extracellular iron inhibited uptake in a buffer at pH 5.5 but not at pH 7.4. Cells treated with the iron chelator deferoxamine displayed higher levels of the iron transporter divalent metal transporter 1 (DMT1) mRNA and protein, and consistent with increased DMT1 expression, the treated cells displayed greater uptake of Pb in the buffer at pH 5.5 but not at pH 7.4. Alternatively at pH 7.4, the transport of Pb was blocked by the anion transporter inhibitor 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid (DIDS), which bound to cell surface proteins at concentrations that were similar to those that blocked Pb uptake. DIDS did not inhibit uptake of Pb n the buffer at pH 5.5. Greater uptake of Pb was observed in a buffer containing sodium bicarbonate, which was abrogated in the presence of DIDS. In summary, the astroglial cell line displays two distinct pH sensitive transport mechanisms for Pb.
© 2004 Society of Toxicology
Neurotoxicology
Different Mechanisms Mediate Uptake of Lead in a Rat Astroglial Cell Line
2 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University; Kennedy-Krieger Institute, Baltimore, MD, 21205
3 Kennedy-Krieger Institute, Baltimore, MD, 21205
4 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University; Department of Preventive Medicine, Soonchunhyan University, Chunan City, Korea
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