Effects of extracellular atp on hepatic fatty acid metabolism.
Guzm[acute]an, Manuel, Guillermo Velasco, and Jos[acute]e Castro.
Department of Biochemistry and Molecular Biology I, Faculty of
Biology, Complutense University, 28040-Madrid, Spain
APStracts 2:0192G, 1995.
Incubation of rat hepatocytes with extracellular ATP inhibited acetyl
-CoA carboxylase (ACC) activity and fatty acid synthesis de novo, with
a concomitant decrease of intracellular malonyl-CoA concentration.
However, both carnitine palmitoyltranferase I (CPT-I) activity and
ketogenesis from palmitate were inhibited in parallel by
extracellular ATP. The inhibitory effect of extracellular ATP on ACC
and CPT-I activities was not evident in Ca2+-depleted hepatocytes.
Incubation of hepatocytes with thapsigargin, 2,5-di-(tert-butyl)-1,4
-benzohydroquinone (BHQ) or A23187, compounds that increase cytosolic
free Ca2+ concentration ([Ca2+]i), depressed ACC activity, whereas
CPT-I activity was unaffected. The phorbol ester 4[beta]-phorbol
12[beta]-mirystate 13[alpha]-acetate (PMA) increased ACC activity,
whereas it decreased CPT-I activity in a non-additive manner with
respect to extracellular ATP. The inhibitory effect of extracellular
ATP on ACC activity was also evident in the presence of
bisindolylmaleimide, a specific inhibitor of protein kinase C (PKC),
whereas this compound abolished the extracellular ATP-mediated
inhibition of CPT-I. In addition, the PMA-induced inhibition of CPT-I
was not potentiated by thapsigargin, BHQ or A23187. Results thus show
(i) that the intracellular concentration of malonyl-CoA is not the
factor responsible for the inhibition of hepatic long-chain fatty
acid oxidation by extracellular ATP, and (ii) that the inhibition of
ACC by extracellular ATP may be mediated by an elevation of [Ca2+]i,
whereas CPT-I may be inhibited by extracellular ATP through a PKC
-dependent mechanism.
Received 9 February 1995; accepted in final form 16 September
1995.
APS Manuscript Number G58-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95