Very-Long-Chain Fatty Acid Metabolism in Adrenoleukodystrophy Protein-Deficient Mice

Takeshi Yamada, Nobue Shinnoh, Akira Kondo, Atsushi Uchiyama, Nobuyuki Shimozawa, Jun Ichi Kira, Takuro Kobayashi

研究成果: Contribution to journalArticle査読

8 被引用数 (Scopus)

抄録

X-linked adrenoleukodystrophy (X-ALD) is characterized by progressive mental and motor deterioration, with demyelination of the central and peripheral nervous system. Its principal biochemical abnormality is the accumulation of very-long-chain fatty acids (VLCFAs) in tissues and body fluids, caused by the impairment of peroxisomal β-oxidation. The authors have generated a line of mice deficient in ALD protein (ALDP) by gene targeting. ALDP-deficient mice appeared normal clinically, at least up to 12 mo. Western blot analysis showed absence of ALDP in the brain, spinal cord, lung, and kidney. The amounts of C26:0 increased by 240% in the spinal cord. VLCFA β-oxidation in cultured hepatocytes was reduced to 50% of normal. The authors investigated the roles of ALDP in VLCFA β-oxidation using the ALDP-deficient mice. Very-long-chain acyl-CoA synthetase (VLACS) is functionally deficient in ALD cells. The impairment of VLCFA β-oxidation in the ALDP-deficient fibroblasts was not corrected by over-expression of VLACS only, but was done by co-expression of VLACS and ALDP, suggesting that VLACS requires ALDP to function. VLACS was detected in the peroxisomal and microsomal fractions of the liver from both types of mice. Peroxisomal VLACS was clearly decreased in the ALDP-deficient mouse. Thus, ALDP is involved in the peroxisomal localization of VLACS.

本文言語英語
ページ(範囲)239-246
ページ数8
ジャーナルCell Biochemistry and Biophysics
32
DOI
出版ステータス出版済み - 2000

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 細胞生物学

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