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Baicalein 5,6,7‐trimethyl ether activates peroxisomal but not mitochondrial fatty acid β‐oxidation
Author(s) -
Morita M.,
Kanai M.,
Mizuno S.,
Iwashima M.,
Hayashi T.,
Shimozawa N.,
Suzuki Y.,
Imanaka T.
Publication year - 2008
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-008-0857-2
Subject(s) - peroxisome , peroxisomal disorder , zellweger syndrome , beta oxidation , adrenoleukodystrophy , chemistry , palmitic acid , fatty acid , carnitine , biochemistry , mitochondrion , gene
Summary Recently, we reported that baicalein 5,6,7‐trimethyl ether (BTM), a flavonoid, is capable of activating fatty acid β‐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 β‐oxidation. We first analysed the effect of BTM on fatty acid β‐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 ) β‐oxidation in the fibroblasts was stimulated by treatment with BTM, except for Zellweger fibroblasts. In contrasts, palmitic acid (C 16:0 ) β‐oxidation was increased (2.8‐fold) only in CACT‐deficient fibroblasts. In U87 glioblastoma cells, C 24:0 β‐oxidation was also activated by treatment with BTM but C 16:0 β‐oxidation was not. The C 16:0 β‐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 β‐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.