HEPATIC a2m-GLOBULIN: A POTENTIAL METABOLIC ROLE IN THE RAT PROXIMAL
TUBULE.
Borkan, Steven C., Y-H Wang, Kelvin T. Lam, Peter Brecher and John H.
Schwartz.
Departments of Medicine and Biochemistry and Thorndike Memorial Laboratory,
Renal Section, Boston City Hospital, Boston University Medical Center, Boston,
Massachusetts, 02118-2999.
APStracts 3:0083F, 1996.
In the present study, we provide immunohistochemical and immunologic evidence
to localize an abundant, 15.5 kDa protein to the soluble protein fraction of
the proximal tubule. This 15.5 kDa protein binds fatty acids in vitro and has
identity with amino acids 10-117 of a2m-globulin (A2), a 19 kDa protein
synthesized predominantly in the male liver. Using RT-PCR, mRNA for A2 was
detected in male liver but not in the male kidney. De novo accumulation of the
15.5 kDa protein was observed in the renal cortex of female rats given
intravenous injections of purified 19 kDa protein (A2), suggesting intra-renal
processing of the larger protein. The potential role of this protein in the
proximal tubule, a site that utilizes fatty acids as an important metabolic
substrate, was determined in isolated proximal tubule segments. Fatty acid and
glucose oxidation rates were measured in three experimental models in which
the 15.5 kDa protein was virtually absent: (1) uninephrectomized male rats
treated with deoxycorticosterone acetate (DOC) and salt; (2) male rats
subjected to bilateral adrenalectomy and (3) normal female rats. In the
absence of the 15.5 kDa protein, fatty acid oxidation rates decreased by 30-
55% whereas glucose oxidation significantly increased in all three models. In
female renal cortex, depletion of the 15.5 kDa protein was associated with a
rise in hFABP, an alternative intracellular transporter of fatty acids. These
data support the hypothesis that a proteolytic cleavage product of hepatic
a2m-globulin may facilitate the oxidation of oleate, a hydrophobic ligand, in
the proximal tubule.
Received 18 December 1995; accepted in final form 18 April 1996.
APS Manuscript Number F419-5.
Article publication pending Am. J. Physiol. (Renal, Fluid, Elect. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96