CONTROL OF THYMIDINE KINASE DURING LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY

To elucidate the molecular basis for the periodic change of thymidine kinase (TK) activity, the expressions of TK protein and TK mRNA were e xamined during liver regeneration. TK protein level, quantified by imm unoblotting assay using the polyclonal antiserum against rat TK polype ptide produced in Escherichia coli, increased 13-fold compared with th e normal at 24 h after partial hepatectomy. This was closely correlate d with a Ii-fold increase in TK activity. Northern blot analysis showe d that the partial hepatectomy caused 12- and 8-fold increase in 2.6 k b 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 norma l base level. This reduction was coupled with a similar decrease in th e 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, p henoxybenzamine, calcium channel blocker, nifedipine or calmodulin inh ibitor, trifluoperazine was also found to inhibit TK activity by the r epression of its mRNA level.