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Acute nephrotoxicity of a carcinogenic iron chelate Selective inhibition of a proteolytic conversion of α 2U ‐globulin to the kidney fatty acid‐binding protein
Author(s) -
Uchida Koji,
Fukuda Aya,
Kawakishi Shunro,
Toyokuni Shinya,
Hiai Hiroshi,
Ikeda Saiko,
Horio Fumihiko
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01330-4
Subject(s) - nephrotoxicity , chemistry , kidney , globulin , fatty acid binding protein , biochemistry , albumin , carcinogen , endocrinology , biology , gene
The mechanism of acute nephrotoxicity of an iron chelate in vivo has been investigated. Administration of a renal carcinogen ferric nitrolotriacetate (Fe‐NTA) (15 mg Fe/kg body weight, intraperitoneally) led to selective loss of a renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa protein by NH 2 ‐terminal sequence demonstrated its identity over 16 NH 2 ‐terminal residues as a kidney fatty acid‐binding protein (k‐FABP) that is a proteolytically modified form of α 2U ‐globulin, a major urinary protein of adult male rats. An immunochemical study using anti‐ α 2U ‐globulin polyclonal antibodies confirmed that a single injection of Fe‐NTA led to a decrease in k‐FABP levels. However, a 19‐kDa protein identical to the α 2U ‐globulin progressively appeared in the kidney, suggesting that the proteolytic processing of α 2U ‐globulin in the renal proximal tubules was suppressed by the treatment with Fe‐NTA. By monitoring k‐FABP and its precursor α 2U ‐globulin, it was determined that repeated exposure to Fe‐NTA caused suppression of both proteolytic and endocytotic activity of the kidney. The implications of these data in relation to the nephrotoxicity of Fe‐NTA are discussed.