Adrenoleukodystrophy: the restoration of peroxisomal beta-oxidation by transfection of normal cDNA.
In order to elucidate the function of ALDP [a protein encoded by the gene responsible for adrenoleukodystrophy (ALD)], normal ALDP cDNA, inserted in an expression vector driven by chicken beta-actin promotor, was transfected into ALD fibroblasts. In a transient expression system, the fatty acid composition did not change even though the ALDP was newly synthesized based on the findings of a western blot analysis. In a stable expression system, 3 cell lines were strongly positive for ALDP. In these cells the level of very long chain fatty acid (C26:0) turned out to be as low as those of the control, while the activities of C24 beta-oxidation, as checked by two different methods, became normal. From these results, it is concluded that ALDP is indispensable for the function of peroxisomal beta-oxidation, and thus the treatment of ALD may be possible by the supplementation of ALDP.
Shinnoh
N
N
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yamada
T
T
Yoshimura
T
T
Furuya
H
H
Yoshida
Y
Y
Suzuki
Y
Y
Shimozawa
N
N
Orii
T
T
Kobayashi
T
T
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000199:Actins / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D002478:Cells, Cultured; D002645:Chickens; D018076:DNA, Complementary; D005227:Fatty Acids / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis*; D008830:Microbodies / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D012016:Reference Values; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D000199:Actins; D018076:DNA, Complementary; D005227:Fatty Acids; D008565:Membrane Proteins; D011994:Recombinant Proteins