INDUCTION OF HEAT-SHOCK PROTEIN-70 AND NUCLEOLIN AND THEIR INTRACELLULAR-DISTRIBUTION DURING EARLY-STAGE OF LIVER-REGENERATION

Our previous work demonstrated a simultaneous induction of Hsp70 and n ucleolin mRNA during the prereplicative stage of hepatocytes after par tial hepatectomy [Ohmori, H. et al. (1990) Exp. Cell Res. 189, 227-232 ]. In the present study, changes of intracellular localization of thes e proteins were examined. Nucleolin, which mainly localized in the nuc leus, increased with time and accumulated in the nucleolus around 12-1 8 h after partial hepatectomy. Hsp70 protein also increased slightly a round 6-12 h after the operation. In accordance with this increase, im munohistochemical staining revealed that almost all nuclei of hepatocy tes became Hsp70-positive, although Hsp70 was seen to be dispersed thr oughout the nucleoplasm and nucleolus at all times examined. Next, we isolated a cDNA clone of ribosomal protein (S-17) and examined its beh avior. Induction of S-17 mRNA was observed to be essentially similar t o that of nucleolin mRNA in regenerating rat liver, although induction s of histone H2A and H4 occurred at a later time, that is, in parallel with DNA synthesis. Furthermore, we observed a simultaneous induction of Hsp70 and nucleolin mRNA by serum-stimulation after serum-depletio n in HeLa and IAR-20 (rat) culture cells. These results suggest that t he induction of Hsp70, in addition to nucleolin, was not fortuitous bu t may be involved in the early events of liver regeneration.