PROTEIN-SYNTHESIS AND GENE-EXPRESSION IN TRANSPLANTED AND POSTISCHEMIC LIVERS

The expression of some genes has been comparatively studied in transpl anted rat liver and in liver reperfused after ischemia in situ. Experi ments on protein synthesis by tissue slices from cold-stored or transp lanted livers show that rat livers that retain a good capacity for pro tein synthesis during storage undergo a profound impairment in the cap acity for protein synthesis during the first hours after transplantati on. This recovers in the following hours. There is never any indicatio n of synthesis of stress proteins, and of hsp 70 in particular. The st eady-state level of mRNAs for albumin, transferrin, and beta-actin, wh ich are well expressed in reperfused postischemic livers in vivo, are reduced early after transplantation and recover only many hours later. Run-on analysis shows that an early defect in transcription and a par tial recovery of this process later on are responsible for these chang es. The steady-state levels of the same mRNAs are well maintained in d onor livers preserved in University of Wisconsin solution for at least 12 hr, and less satisfactorily in Euro-Collins solution. Results of r un-on analysis parallel the data on mRNA levels. The behavior of these mRNAs is, therefore, clearly different in reperfused and transplanted liver. The early stages of liver transplantation seem to be character ized by a depressed capacity of gene expression, without the reactive phenomenon of activation of stress protein genes that occurs in reperf used postischemic livers.