Age-associated changes in rat hepatocytes: Studies of the character of a polypeptide subject to diminished synthesis at an early age

Abstract

We have previously reported the observation of an age-dependent aberration in synthesis of a 20000 MW polypeptide (P20000) by isolated hepatocytes. Studies of the post-synthetic distribution of P20000 within the hepatocyte establish that the bulk of P20000 synthesized in vitro remains in association with the endoplasmic reticulum, or can be isolated with the microsomes derived therefrom. No evidence was obtained for an accrual with time of P20000 by the nucleus, mito. chondria or cell sap. An accumulation of P20000 in the secreted protein fraction was observed, but the net secretion of P20000 with time was found to be only a minor fraction of that predictable from the extent of labeling of the microsomal complement of P20000. This result is in sharp contrast to simultaneous measurements of the secretion of albumin. Stability of the radioisotope content of P20000 in the presence of cycloheximide precludes turnover or degradation as a basis for these observations. It is concluded that P20000 is a protein of the liver endoplasmic reticulum. Comparison of hepatocytes from male and female animals establishes that synthesis of P20000 is a property of the male animal.