TY - JOUR
T1 - Induction of hepatic acyl-CoA-binding protein and liver fatty acid-binding protein by perfluorodecanoic acid in rats. Lack of correlation with hepatic long-chain acyl-CoA levels
AU - Sterchele, Paul F.
AU - Vanden Heuvel, John P.
AU - Davis, John W.
AU - Shrago, Earl
AU - Knudsen, Jens
AU - Peterson, Richard E.
N1 - Funding Information:
Acknowledgements--We acknowledge the excellent technical assistance of Dorothy Nesbit, Jamie Hermus, and Jill Sadler. We also thank Terry Spennetta for valuable advice pertaining to the HPLC analysis of long-chain acyl-CoA esters. Generous contributions of antibodies were made by T. Hashimoto (Shinshu University School of Medicine, Japan) and E. Costa and A. Guidotti (Fidio-Georgetown Institute for the Neurosciences, Washington, DC). We also extend our gratitude to T. Yamamoto (Tohoku University, Japan) and W. Mellon (University of Wisconsin, Madison) for cDNA donations. This work was supported by NIH Grant GM 41131.
PY - 1994/8/30
Y1 - 1994/8/30
N2 - Liver fatty acid-binding protein (L-FABP) and acyl-CoA-binding protein (ACBP) are involved in the intracellular trafficking and compartmentalization of fatty acids and fatty acyl-CoA esters, respectively, in the liver. Both proteins are induced in rat liver by the potent peroxisome proliferator perfluorodecanoic acid (PFDA). While it is believed that the peroxisome proliferator-activated receptor may mediate the responses to peroxisome proliferators by inducing responsive genes, the ligand(s) of this receptor remains unknown. We hypothesized that induction of L-FABP and ACBP in rat liver by PFDA is secondary to accumulation of long-chain acyl-CoA esters. However, neither dose-response nor time-course effects of PFDA on hepatic long-chain acyl-CoA, L-FABP, or ACBP concentrations confirmed this hypothesis. In a dose-response study, PFDA increased hepatic long-chain acyl-CoA concentrations (7 days after treatment) over the dose range of 20-50 mg/kg, whereas it increased ACBP and L-FABP over the wider dose range of 20-65 mg/kg. In the time-course study, PFDA treatment (50 mg/kg) elevated long-chain acyl-CoA esters in the liver beginning on day 3 post-treatment, yet hepatic L-FABP concentrations were increased earlier beginning on day 2 and ACBP was not induced until day 7. To determine if this dissociation of increases in hepatic long-chain acyl-CoA concentrations from increases in hepatic L-FABP and ACBP concentrations could be demonstrated under other conditions, control rats fasted for 24-48 hr were used. Fasting increased hepatic long-chain acyl-CoA levels to a greater extent than PFDA treatment, yet neither L-FABP nor ACBP was induced. We conclude that elevated concentrations of hepatic long-chain acyl-CoAs in PFDA-treated rats are not a major contributor to the induction of L-FABP or ACBP by peroxisome proliferators. A more plausible mechanism is that PFDA induces L-FABP and ACBP by activating the peroxisome proliferator receptor directly rather than indirectly through long-chain acyl-CoA esters.
AB - Liver fatty acid-binding protein (L-FABP) and acyl-CoA-binding protein (ACBP) are involved in the intracellular trafficking and compartmentalization of fatty acids and fatty acyl-CoA esters, respectively, in the liver. Both proteins are induced in rat liver by the potent peroxisome proliferator perfluorodecanoic acid (PFDA). While it is believed that the peroxisome proliferator-activated receptor may mediate the responses to peroxisome proliferators by inducing responsive genes, the ligand(s) of this receptor remains unknown. We hypothesized that induction of L-FABP and ACBP in rat liver by PFDA is secondary to accumulation of long-chain acyl-CoA esters. However, neither dose-response nor time-course effects of PFDA on hepatic long-chain acyl-CoA, L-FABP, or ACBP concentrations confirmed this hypothesis. In a dose-response study, PFDA increased hepatic long-chain acyl-CoA concentrations (7 days after treatment) over the dose range of 20-50 mg/kg, whereas it increased ACBP and L-FABP over the wider dose range of 20-65 mg/kg. In the time-course study, PFDA treatment (50 mg/kg) elevated long-chain acyl-CoA esters in the liver beginning on day 3 post-treatment, yet hepatic L-FABP concentrations were increased earlier beginning on day 2 and ACBP was not induced until day 7. To determine if this dissociation of increases in hepatic long-chain acyl-CoA concentrations from increases in hepatic L-FABP and ACBP concentrations could be demonstrated under other conditions, control rats fasted for 24-48 hr were used. Fasting increased hepatic long-chain acyl-CoA levels to a greater extent than PFDA treatment, yet neither L-FABP nor ACBP was induced. We conclude that elevated concentrations of hepatic long-chain acyl-CoAs in PFDA-treated rats are not a major contributor to the induction of L-FABP or ACBP by peroxisome proliferators. A more plausible mechanism is that PFDA induces L-FABP and ACBP by activating the peroxisome proliferator receptor directly rather than indirectly through long-chain acyl-CoA esters.
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U2 - 10.1016/0006-2952(94)90366-2
DO - 10.1016/0006-2952(94)90366-2
M3 - Article
C2 - 8093108
AN - SCOPUS:0028094479
VL - 48
SP - 955
EP - 966
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 5
ER -