A comparison of male rat and human urinary proteins: Implications for human resistance to hyaline droplet nephropathy

摘要: Abstract α 2u -Globulin (αG), the major urinary protein of sexually mature male rats, is a key determinant susceptibility to hyaline droplet nephropathy (HDN) induced by variety hydrocarbons in rats. Arguments against extrapolating renal toxicity and carcinogenicity data for HDN-inducing toxicants from rats risk assessment humans rely on observation that do not express αG. Yet, human serum urine are known contain proteins coded same gene family also controls αG synthesis rat. Therefore, understand some quantitative qualitative differences between rat which confer apparent resistance HDN humans, F344 (ca. 3 months old) normal males were compared cation exchange, gel filtration, SDS-PAGE, partially identified Western blotting. We observed (1) content only 1% urine; (2) proteins, recovered (NH 4 ) 2 SO precipitation followed dialysis, primarily high (≥75 kDa) molecular weight (MW) with minor components 12–66 kDa; (3) has little high-MW protein, but rich (18.5 kDa); (4) at pH 5, most cationic fraction constituted about 4% total while analogous urine, containing αG, contained 26% protein; (5) (at 5.0) included small amounts e.g., 1 -acid glycoprotein, -microglobulin, products coding Thus, although excrete trace similar very low relatively proportion MW abundant form biological basis suggesting type fuel solvent hydrocarbon-induced nephropathy, sequelae such