AGE-RELATED-CHANGES IN PROLIFERATING CELL NUCLEAR ANTIGEN LEVELS

To clarify the effect of aging on rat liver regeneration, we compared proliferating eel nuclear antigen (PCNA) levels in control and regener ating livers from young and aged rats 48 h after partial hepatectomy. The nucleoplasm and cytoplasm from regenerating livers of 2-month and 24 month-old rats were fractionated by phosphocellulose column chromat ography, aliquots of fractions were transferred to nitrocellulose filt ers and the amounts of PCNA in each fraction were measured by an immun ostaining method. Two forms of PCNA, L type (eluted at low concentrati ons of KCl) and H type (eluted at high KCl concentrations) were observ ed in the nucleoplasm from both control and regenerating young rat liv er. On the other hand, the cytoplasm contained P type (eluted in the p ass-through fraction), L type and H type PCNA. In control liver from a ged rats, three types of PCNA in the cytoplasmm and two types in the n ucleoplasm were present at decreased levels. In regenerating liver fro m young rats, the increases in L type in the cytoplasm and H type in t he nucleoplasm were remarkable. However, none of the three PCNA types increased significantly during liver regeneration in aged rats. Treatm ent with DNase resulted in the disappearance of the H type with a conc omitant increase in the P and L types. These results suggest that the H type is a complex form consisting of the P and L types of PCNA and D NA. These results suggest that the increase in the L type in the cytop lasm reflects newly synthesized PCNA production for cellular prolifera tion and that the increase in the H type in the nucleoplasm is a refle ction of binding to DNA and the fundamental role of PCNA itself in liv er regeneration in young rats. On the other hand, there was little inc rease in any of the three types in regenerating liver from 24-month-ol d rats. Thus, PCNA content may be closely related to the decrease in t he rate of cellular proliferation in aged animals. Copyright (C) 1996 Elsevier Science Ireland Ltd.