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The lipocalin 2 receptor is expressed in kidney proximal tubule cells and mediates cadmium‐metallothionein uptake and apoptosis
Author(s) -
Thevenod Frank,
Langelüddecke Christian,
Lee WingKee,
Wolff Natascha A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.839.9
Chronic exposure to cadmium (Cd) damages the kidney partly via megalin:cubilin–dependent receptor‐mediated endocytosis (RME) of Cd‐metallothionein (MT) complexes by renal proximal tubular cells (PTC) which results in apoptosis. A cell‐surface receptor for lipocalin 2 (24p3, NGAL) has been cloned, a secreted protein that binds to iron‐containing bacterial siderophores. Interestingly, the lipoclain 2 receptor (Lip2R) is also expressed in the kidney. Lip2R is expressed in cultured rat PTC (WKPT‐0293. Cl.2) and immunofluorescence microscopy (IF) also detected Lip2R in plasma membranes (PM). We hypothesized that Lip2R contributes to CdMT uptake and toxicity in PTC. Indeed, lipocalin 2 reduced CdMT toxicity in PTC. IF and confocal laser scanning microscopy of transiently transfected CHO cells demonstrated PM localization of Lip2R. Apoptosis by CdMT was observed in Lip2R‐transfected cells only. CdMT toxicity saturated at 24 h and 1.4μM MT/10 μM Cd2+. At this MT concentration the kinetics of Alexa546‐MT uptake mirrored those of CdMT toxicity. In conclusion, CdMT is a ligand of the Lip2R which, in addition to megalin:cubilin, mediates RME of CdMT and death in kidney PTC. Funded by DFG TH345/11‐1.