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 have investigated a possible mechanism whereby the presence of the Walker 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I), generally accepted as the main site of regulation of fatty acid oxidation, was unaffected by the presence of the extra-hepatic tumour. However, mitochondrial inner-membrane carnitine palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immuno-detection by Western blotting using a CPT II-specific antibody identified two bands (corresponding to M(r) 69,000 and 54,000) in tumour-bearing rats whereas only the normal-sized CPT II was present (at the expected M(r) 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalytically less active protein that arises in vivo, since its appearance was not affected by the inclusion of proteolysis inhibitors in the mitochondrial preparation buffers. Treatment of the tumour-bearing rats with indomethacin, a prostaglandin (including PGE2) synthesis inhibitor, increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE2 may play a role in the control of CPT II expression in the liver of tumour-bearing rats. Indomethacin treatment did not affect either of the two CPT activities of the mitochondria isolated from tumour tissue.
Seelaender
M C
MC
Departamento de Histologia e Embryologia, Cidade Universitária, São Paulo, Brasil.
Curi
R
R
Colquhoun
A
A
Williams
J F
JF
Zammitt
V A
VA
D000818:Animals; D002100:Cachexia / Q000201:enzymology* / Q000473:pathology; D002279:Carcinoma 256, Walker / Q000201:enzymology* / Q000473:pathology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology*; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar
D002334:Carnitine O-Palmitoyltransferase; D015232:Dinoprostone; D007213:Indomethacin