Control of thymidine kinase during liver regeneration after partial hepatectomy

Abstract

To elucidate the molecular basis for the periodic change of thymidine kinase (TK) activity, the expressions of TK protein and TK mRNA were examined during liver regeneration. TK protein level, quantified by immunoblotting assay using the polyclonal antiserum against rat TK polypeptide produced in Escherichia coli, increased 13-fold compared with the normal at 24 h after partial hepatectomy. This was closely correlated with a 11-fold increase in TK activity. Northern blot analysis showed that the partial hepatectomy caused 12 and 8-fold increase in 2.6 kb and 1.1 kb TK mRNA at 24 h after surgery, respectively. During next 12 h the levels of both TK mRNA species reduced to 5-fold of the normal base level. This reduction was coupled with a similar decrease in the activity as well as in the amount of TK protein. The TK mRNA levels were strictly proportional to the levels of TK activity and TK protein at 48 h and 72 h after partial hepatectomy. These results demonstrate that the change in TK activity is controlled at the mRNA level during liver regeneration. The injection of alpha-adrenoceptor antagonist, phenoxybenzamine, calcium channel blocker, nifedipine or calmodulin inhibitor, trifluoperazine was also found to inhibit TK activity by the repression of its mRNA level.