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摘要
The purpose of this study is to establish an assay method to screen for chemical compounds that stimulate peroxisomal fatty acid beta-oxidation activity in X-linked adrenoleukodystropy (X-ALD) fibroblasts. In this investigation, we used 12-(1-pyrene)dodecanoic acid (pyrene-C12:0), a fluorescent fatty acid analog, as a substrate for fatty acid beta-oxidation. When human skin fibroblasts were incubated with pyrene-C12:0, beta-oxidation products such as pyrene-C10:0 and pyrene-C8:0 were generated time-dependently. These beta-oxidation products were scarcely detected in the fibroblasts from patients with Zellweger syndrome, a peroxisomal biogenesis disorder. In contrast, in fibroblasts with mitochondrial carnitine-acylcarnitine translocase deficiency, the beta-oxidation products were detected at a level similar to control fibroblasts. These results indicate that the beta-oxidation of pyrene-C12:0 takes place in peroxisomes, but not mitochondria, so pyrene-C12:0 is useful for measuring peroxisomal fatty acid beta-oxidation activity. In X-ALD fibroblasts, the beta-oxidation activity for pyrene-C12:0 was approximately 40 % of control fibroblasts, which is consistent with previous results using [1-C-14]lignoceric acid as the substrate. The present study provides a convenient procedure for screening chemical compounds that stimulate the peroxisomal fatty acid beta-oxidation in X-ALD fibroblasts.
- 出版日期2016-9
