Baicalein 5,6,7-trimethyl ether activates peroxisomal but not mitochondrial fatty acid beta-oxidation

J Inherit Metab Dis. 2008 Jun;31(3):442-9. doi: 10.1007/s10545-008-0857-2. Epub 2008 May 9.

Abstract

Recently, we reported that baicalein 5,6,7-trimethyl ether (BTM), a flavonoid, is capable of activating fatty acid beta-oxidation in X-linked adrenoleukodystrophy (X-ALD) fibroblasts (FEBS Lett. 2005; 579: 409-414). The objective of this study was to clarify whether BTM activates peroxisomal and/or mitochondrial fatty acid beta-oxidation. We first analysed the effect of BTM on fatty acid beta-oxidation in fibroblasts derived from healthy controls as well as patients with X-ALD, mitochondrial carnitine-acylcarnitine translocase (CACT) deficiency, and peroxisome biogenesis disorder, Zellweger syndrome. Lignoceric acid (C(24:0)) beta-oxidation in the fibroblasts was stimulated by treatment with BTM, except for Zellweger fibroblasts. In contrasts, palmitic acid (C(16:0)) beta-oxidation was increased (2.8-fold) only in CACT-deficient fibroblasts. In U87 glioblastoma cells, C(24:0) beta-oxidation was also activated by treatment with BTM but C(16:0) beta-oxidation was not. The C(16:0) beta-oxidation was, however, significantly increased in the presence of 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a carnitine palmitoyltransferase I inhibitor. These results indicate that BTM activates peroxisomal but not mitochondrial fatty acid beta-oxidation. In addition, we found that BTM did not upregulate the expression of ABCD2/ALDR, ABCD3/PMP70, ACOX1 and FATP4 genes but slightly increased ACSVL1 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D
  • ATP-Binding Cassette Transporters / genetics
  • Adrenoleukodystrophy / metabolism
  • Carnitine Acyltransferases / deficiency
  • Cells, Cultured
  • Coenzyme A Ligases / genetics
  • Epoxy Compounds / pharmacology
  • Fatty Acids / metabolism*
  • Fibroblasts / metabolism
  • Flavanones / pharmacology*
  • Glioblastoma / metabolism
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Peroxisomes / drug effects*
  • Peroxisomes / metabolism
  • Zellweger Syndrome / metabolism

Substances

  • ABCD2 protein, human
  • ABCD3 protein, human
  • ATP Binding Cassette Transporter, Subfamily D
  • ATP-Binding Cassette Transporters
  • Epoxy Compounds
  • Fatty Acids
  • Flavanones
  • baicalein 5,6,7-trimethyl ether
  • ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate
  • Carnitine Acyltransferases
  • Coenzyme A Ligases