HEPATIC ALPHA(2-MU)-GLOBULIN - A POTENTIAL METABOLIC ROLE IN THE RAT PROXIMAL TUBULE

In the present study, we provide immunohistochemical and immunologic e vidence to localize an abundant, 15.5-kDa protein to the soluble prote in fraction of the proximal tubule. This 15.5-kDa protein binds fatty acids in vitro and has identity with amino acids 10-117 of alpha(2 mu) -globulin (A(2) fragment), a 19-kDa protein synthesized predominantly in the male liver. With reverse transcription-polymerase chain reactio n, mRNA for A(2) was detected in male liver but not in the male kidney . De novo accumulation of the 15.5-kDa protein was observed in the ren al cortex of female rats given intravenous injections of purified 19-k Da protein (A(2)), suggesting intrarenal processing of the larger prot ein. The potential role of this protein in the proximal tubule, a site that utilizes fatty acids as an important metabolic substrate, was de termined in isolated proximal tubule segments. Fatty acid and glucose oxidation rates were measured in three experimental models in which th e 15.5-kDa protein was virtually absent: 1) uninephrectomized male rat s treated with deoxycorticosterone acetate and salt, 2) male rats subj ected to bilateral adrenalectomy, and 3) normal female rats. In the ab sence of the 15.5-kDa protein, fatty acid oxidation rates decreased by 30-55%, whereas glucose oxidation significantly increased in all thre e models. In female renal cortex, depletion of the 15.5-kDa protein wa s associated with a rise in heart fatty acid binding protein, an alter native intracellular transporter of fatty acids. These data support th e hypothesis that a proteolytic cleavage product of hepatic alpha(2 mu )-globulin may facilitate the oxidation of oleate, a hydrophobic ligan d, in the proximal tubule.