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

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.

• Authors: M Morita, M Kanai, S Mizuno, M Iwashima, T Hayashi, N Shimozawa, Y Suzuki, T Imanaka
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 31 Issue 3 Pg. 442-9 (Jun 2008) ISSN: 1573-2665 [Electronic] United States
• PMID: 18470630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, metabolism)
• Oxidation-Reduction
• Peroxisomes (drug effects, metabolism)
• Zellweger Syndrome (metabolism)