CARNITINE PALMITOYLTRANSFERASE-II ACTIVITY IS DECREASED IN LIVER-MITOCHONDRIA OF CACHECTIC RATS BEARING THE WALKER-256 CARCINOSARCOMA - EFFECT OF INDOMETHACIN TREATMENT

The syndrome of cancer cachexia is accompanied by several alterations of lipid metabolism, especially that in the liver. In this study we ha ve investigated a possible mechanism whereby the presence of the Walke r 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine pa lmitoyltransferase I (CPT I), generally accepted as the main site of r egulation of fatty acid oxidation, was unaffected by the presence of t he extra-hepatic tumour. However, mitochondrial inner-membrane carniti ne palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immune-d etection by Western blotting using a CPT II-specific antibody identifi ed two bands (corresponding to M-r 69,000 and 54,000) in tumour-bearin g rats whereas only the normal-sized CPT II was present (at the expect ed M-r 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalyti cally less active protein that arises in vivo, since its appearance wa s not affected by the inclusion of proteolysis inhibitors in the mitoc hondrial preparation buffers. Treatment of the tumour-bearing rats wit h indomethacin, a prostaglandin (including PGE(2)) synthesis inhibitor , increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE(2) may play a role in th e control of CPT II expression in the liver of tumour-bearing rats. In domethacin treatment did not affect either of the two CPT activities o f the mitochondria isolated from tumour tissue.