Selective left-lobe atrophy by nodularin treatment accompanied by reduced protein phosphatase 1/2A and increased peroxisome proliferation in rat liver

The effect of nodularin on selective atrophy of left lobes in the liver was investigated in F344 rats. Nodularin was injected for 10 weeks from the th ird week of initiation with saline or N-nitrosodiethylamine (DEN), grouped as SIN and DIN, respectively. Nodularin significantly decreased weights of left (LL) and caudate (CL) lobes but increased right (RL) and middle (ML) r obes in SIN rats, Activity of protein phosphatases [types I (PPI) and 2A (P P2A)] was more severely reduced in S/N than D/N rats; moreover, in LL compa red with RL of S/N rats, activity was significantly inhibited by nodularin treatment from week 4, which corresponded to 2 weeks after nodularin inject ion. However, nodularin significantly induced peroxisomal palmitoyl-CoA oxi dase and cytochrome P-450 4AI expression in S/N compared with D/N rats. An effect of nodularin on apoptosis was evident since expression of Bcl-X-S wa s clearly induced in LL of SIN rats as opposed to various Inductions of Bcl -X-L. However, Bcl-X-L in RL was persistently induced, with undetectable Bc l-X-s expression. These results demonstrate biochemical evidence of selecti ve atrophy of LL by inhibition of PPI and PP2A activity, increase of peroxi somal enzymes and induction of Bcl-X-S expression, in contrast to prolifera tion of RL in rats treated with nodularin alone. However, nodularin endowed DEN-altered hepatocytes with regenerating power and concomitant restoratio n of phosphatase activity as well as persistent expression of Bcl-X-L in D/ N rats. (C) 20001 Wiley-Liss, Inc.