TY - JOUR
T1 - Leishmania chagasi
T2 - Uptake of iron bound to lactoferrin or transferrin requires an iron reductase
AU - Wilson, Mary E.
AU - Lewis, Troy S.
AU - Miller, Melissa A.
AU - McCormick, Michael L.
AU - Britigan, Bradley E.
N1 - Funding Information:
This work was supported by Veterans' Affairs Merit Review grants (MEW, BEB, and MLM), and Grants AI32135, AI45540 (MEW), and AI34954 (BEB) from the National Institute of Health.
PY - 2002/3/1
Y1 - 2002/3/1
N2 - Leishmania chagasi can utilize iron bound to transferrin, lactoferrin, or other chelates. We investigated the mechanism of iron uptake. Promastigotes preferentially took up iron in a reduced rather than an oxidized form, suggesting that extracellular iron must be reduced prior to internalization. Similar to literature reports, a 70-kDa protein in promastigote membrane-containing microsomes bound to [125I]-labeled transferrin. However, [125I]lactoferrin and [125I]albumin also bound a similar 70-kDa protein, suggesting that binding might not be specific. Both total and fractionated promastigotes exhibited an NADPH-dependent iron reductase activity. In contrast to trypanosomes, which take up transferrin through a specific receptor, these data support a model in which a parasite-associated or secreted reductase reduces ferric to ferrous iron, decreasing its affinity for the extracellular chelate and allowing it to be readily internalized by the parasite. This could account for the ability of the parasite to utilize iron from multiple sources in diverse host environments.
AB - Leishmania chagasi can utilize iron bound to transferrin, lactoferrin, or other chelates. We investigated the mechanism of iron uptake. Promastigotes preferentially took up iron in a reduced rather than an oxidized form, suggesting that extracellular iron must be reduced prior to internalization. Similar to literature reports, a 70-kDa protein in promastigote membrane-containing microsomes bound to [125I]-labeled transferrin. However, [125I]lactoferrin and [125I]albumin also bound a similar 70-kDa protein, suggesting that binding might not be specific. Both total and fractionated promastigotes exhibited an NADPH-dependent iron reductase activity. In contrast to trypanosomes, which take up transferrin through a specific receptor, these data support a model in which a parasite-associated or secreted reductase reduces ferric to ferrous iron, decreasing its affinity for the extracellular chelate and allowing it to be readily internalized by the parasite. This could account for the ability of the parasite to utilize iron from multiple sources in diverse host environments.
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U2 - 10.1016/S0014-4894(02)00018-8
DO - 10.1016/S0014-4894(02)00018-8
M3 - Article
C2 - 12173405
AN - SCOPUS:0036525476
SN - 0014-4894
VL - 100
SP - 196
EP - 207
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 3
ER -