Ascorbic acid deficiency decreases the renal level of kidney fatty acid- binding protein by lowering the α(2u)-globulin gene expression in liver in scurvy-prone ODS rats

Abstract

The evidence for the role of ascorbic acid in gene expression or protein synthesis in vivo is limited. To investigate this role of ascorbic acid, we surveyed proteins whose tissue levels are changed by ascorbic acid deficiency by using ODS rats with a hereditary defect in ascorbic acid biosynthesis. Male ODS rats (7 wk old, body weight ~130 g) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or an ascorbic acid-free diet for 14 d. Ascorbic acid deficiency decreased a renal protein with an apparent molecular mass of 17 kDa. The amino-terminal amino acid sequence of 16 residues of this 17-kDa protein was identical to a kidney fatty acid-binding protein known to be generated by proteolytic degradation of α(2u)-globulin, a major urinary protein of adult male rats. α(2u)-Globulin is synthesized in liver, secreted into blood and excreted into urine, but partially reabsorbed by renal proximal tubules. It exists in kidney in a proteolytically modified form. Ascorbic acid deficiency lowered the renal level of kidney fatty acid- binding protein to 53% (P < 0.05) and lowered the serum level of α(2u)- globulin to 52% (P < 0.05) of the level of the control group, but did not affect the amount of α(2u)-globulin excreted into urine. The hepatic level of α(2u)-globulin mRNA of the ascorbic acid-deficient rats was significantly lower (30%) than that of the control rats. These results suggest that in male ODS rats, ascorbic acid deficiency decreases the renal level of kidney fatty acid-binding protein by lowering α(2u)-globulin gene expression in liver.