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Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator

(2005) JOURNAL OF CELL BIOLOGY. 169(1). p.93-104
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Abstract
X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disease due to mutations in the ABCD1 (ALD) gene, encoding a peroxisomal ATP-binding cassette transporter (ALDP). Overexpression of adrenoleukodystrophy-related protein, an ALDP homologue encoded by the AB CD2 (adrenoleukodystrophy-related) gene, can compensate for ALDP deficiency. 4-Phenyl-butyrate (PBA) has been shown to induce both ABCD2 expression and peroxisome proliferation in human fibroblasts. We show that peroxisome proliferation with unusual shapes and clusters occurred in liver of PBA-treated rodents in a PPAR alpha-independent way. PBA activated Abcd2 in cultured glial cells, making PBA a candidate drug for therapy of X-ALD. The Abcd2 induction observed was partially PPAR alpha independent in hepatocytes and totally independent in fibroblasts. We demonstrate that a GC box and a CCAAT box of the Abcd2 promoter are the key elements of the PBA-dependent Abcd2 induction, histone deacetylase (HDAC) 1 being recruited by the GC box. Thus, PBA is a nonclassical peroxisome proliferator inducing pleiotropic effects, including effects at the peroxisomal level mainly through HDAC inhibition.
Keywords
HISTONE DEACETYLASE, X-LINKED ADRENOLEUKODYSTROPHY, ACTIVATED RECEPTOR, MEMBRANE-PROTEIN, TRANSCRIPTIONAL REGULATION, EXPRESSION PATTERN, ABC-TRANSPORTER, BETA-OXIDATION, RAT-LIVER, NF-Y

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Chicago
Gondcaille, Catherine, Marianne Depreter, Stéphane Fourcade, Maria Rita Lecca, Sabrina Leclercq, Pascal GP Martin, Thierry Pineau, et al. 2005. “Phenylbutyrate Up-regulates the Adrenoleukodystrophy-related Gene as a Nonclassical Peroxisome Proliferator.” Journal of Cell Biology 169 (1): 93–104.
APA
Gondcaille, C., Depreter, M., Fourcade, S., Lecca, M. R., Leclercq, S., Martin, P. G., Pineau, T., et al. (2005). Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator. JOURNAL OF CELL BIOLOGY, 169(1), 93–104.
Vancouver
1.
Gondcaille C, Depreter M, Fourcade S, Lecca MR, Leclercq S, Martin PG, et al. Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator. JOURNAL OF CELL BIOLOGY. 2005;169(1):93–104.
MLA
Gondcaille, Catherine, Marianne Depreter, Stéphane Fourcade, et al. “Phenylbutyrate Up-regulates the Adrenoleukodystrophy-related Gene as a Nonclassical Peroxisome Proliferator.” JOURNAL OF CELL BIOLOGY 169.1 (2005): 93–104. Print.
@article{326696,
  abstract     = {X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disease due to mutations in the ABCD1 (ALD) gene, encoding a peroxisomal ATP-binding cassette transporter (ALDP). Overexpression of adrenoleukodystrophy-related protein, an ALDP homologue encoded by the AB CD2 (adrenoleukodystrophy-related) gene, can compensate for ALDP deficiency. 4-Phenyl-butyrate (PBA) has been shown to induce both ABCD2 expression and peroxisome proliferation in human fibroblasts. We show that peroxisome proliferation with unusual shapes and clusters occurred in liver of PBA-treated rodents in a PPAR alpha-independent way. PBA activated Abcd2 in cultured glial cells, making PBA a candidate drug for therapy of X-ALD. The Abcd2 induction observed was partially PPAR alpha independent in hepatocytes and totally independent in fibroblasts. We demonstrate that a GC box and a CCAAT box of the Abcd2 promoter are the key elements of the PBA-dependent Abcd2 induction, histone deacetylase (HDAC) 1 being recruited by the GC box. Thus, PBA is a nonclassical peroxisome proliferator inducing pleiotropic effects, including effects at the peroxisomal level mainly through HDAC inhibition.},
  author       = {Gondcaille, Catherine and Depreter, Marianne and Fourcade, St{\'e}phane and Lecca, Maria Rita and Leclercq, Sabrina and Martin, Pascal GP and Pineau, Thierry and Cadepond, Fran\c{c}oise and ElEtr, Martine and Bertrand, Nathalie and Beley, Alain and Duclos, Sandrine and De Craemer, Dirk and Roels, Frank and Savary, St{\'e}phane and Bugaut, Maurice},
  issn         = {0021-9525},
  journal      = {JOURNAL OF CELL BIOLOGY},
  language     = {eng},
  number       = {1},
  pages        = {93--104},
  title        = {Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator},
  url          = {http://dx.doi.org/10.1083/jcb.200501036},
  volume       = {169},
  year         = {2005},
}

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