Decrease of renal phosphoenolpyruvate carboxykinase RNA and poly(A) + RNA level by ochratoxin A

Abstract

Ochratoxin A, a nephrotoxin produced by Aspergillus ochraceus, decreases the activity of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) in the cytosol of rat kidneys, as well as inhibits renal gluconeogenesis ( Meisner, H., and Meisner, P. (1981) Arch. Biochem. Biophys. 208, 146–153). Ochratoxin A greatly reduces the level of translatable mRNA for PEPCK in kidneys of rats fed the toxin for 2 days, while the efficiency of translation of poly(A) + RNA is not affected. A species of poly(A) + RNA coding for a 72,000 M r protein is increased in relative amount. Although similar in molecular weight to PEPCK, this protein is not precipitated by an antibody to PEPCK, and has a different peptide map. The sequence abundance of PEPCK mRNA, as measured by either Northern blotting or the dot blot technique, is reduced, while the hepatic level of PEPCK mRNA is not changed. The total poly(A) + RNA level is reduced 50% in kidneys, but not livers, of rats fed a standard dose of ochratoxin A for 3–5 days. In nuclei isolated from toxin-fed rats, the rate of transcription of total RNA or PEPCK mRNA, as measured by incorporation of [ 32P]UTP, is not reduced by the toxin. Ochratoxin A therefore lowers total renal mRNA concentration, and certain species, notably PEPCK, are reduced to a greater extent than the bulk of the RNA pool.