cDNA Cloning and Genomic Organization of Peroxisome Proliferator-Inducible Long-Chain Acyl-CoA Hydrolase from Rat Liver Cytosol

Yamada, Junji; Suga, Kazutaka; Furihata, Takao; Kitahara, Mari; Watanabe, Takafumi; Hosokawa, Masakiyo; Satoh, Tetsuo; Suga, Tetsuya

doi:10.1006/bbrc.1998.9048

Cited by 20 publications

(16 citation statements)

References 30 publications

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“…Acot1 is regulated by fibrate treatment via PPARa in vivo It has been shown that Acot1 is upregulated at mRNA and protein levels in rodents by treatment with clofibrate (17)(18)(19) and di(2-ethylhexyl) phthalate (21). However, this upregulation at the mRNA level was shown only by Northern blot analysis; to quantitatively examine the level of induction of Acot1 mRNA in mouse liver by Wy-14,643, real-time PCR was carried out using specific primers toward Acot1.…”

Section: Resultsmentioning

confidence: 99%

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The acyl-CoA thioesterase I is regulated by PPARα and HNF4α via a distal response element in the promoter

Dongol

Shah

Kim

et al. 2007

Journal of Lipid Research

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The cytosolic acyl-coenzyme A thioesterase I (Acot1) is an enzyme that hydrolyzes long-chain acyl-CoAs of C 12 -C 20 -CoA in chain length to the free fatty acid and CoA. Acot1 was shown previously to be strongly upregulated at the mRNA and protein level in rodents by fibrates. In this study, we show that Acot1 mRNA levels were increased by 90-fold in liver by treatment with Wy-14,643 and that Acot1 mRNA was also increased by 15-fold in the liver of hepatocyte nuclear factor 4a (HNF4a) knockout animals. Our study identified a direct repeat 1 (DR1) located in the Acot1 gene promoter in mouse, which binds the peroxisome proliferator-activated receptor a (PPARa) and HNF4a. Chromatin immunoprecipitation (ChIP) assay showed that the identified DR1 bound PPARa/retinoid X receptor a (RXRa) and HNF4a, whereas the binding in ChIP was abrogated in the PPARa and HNF4a knockout mouse models.

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Section: Resultsmentioning

confidence: 99%

“…The Acot1 cDNA was initially cloned from rat (21) and was shown to be induced in liver by the peroxisome proliferator di(2-ethylhexyl) phthalate (22). At the same time, the cDNA (17) and gene (19) were cloned from mouse and were also shown to be induced by the peroxisome proliferator clofibrate in liver at both the mRNA and protein levels (18,19).…”

mentioning

confidence: 99%

The acyl-CoA thioesterase I is regulated by PPARα and HNF4α via a distal response element in the promoter

Dongol

Shah

Kim

et al. 2007

Journal of Lipid Research

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“…1 Briefly, 2 g of recombinant ACH2-6His was added to a 750-l assay volume composed of 200 M DTNB (Sigma) in 50 mM potassium phosphate buffer, pH 8.0, acyl-CoA substrate (Sigma and ICN), and BSA (Sigma). AcylCoA stock concentrations were verified by their absorbance at 260 nM in 50 mM potassium phosphate buffer, pH 8.0, using a molar extinction coefficient of 16,400 M Ϫ1 cm Ϫ1 .…”

Section: Methodsmentioning

confidence: 99%

Biochemical and Molecular Characterization of ACH2, an Acyl-CoA Thioesterase from Arabidopsis thaliana

Tilton¹,

Shockey²,

Browse

2004

Journal of Biological Chemistry

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By using computer-based homology searches of the Arabidopsis genome, we identified the gene for ACH2, a putative acyl-CoA thioesterase. With the exception of a unique 129-amino acid N-terminal extension, the ACH2 protein is 17-36% identical to members of a family of acyl-CoA thioesterases that are found in both prokaryotes and eukaryotes. The eukaryotic homologs of ACH2 are peroxisomal acyl-CoA thioesterases that are up-regulated during times of increased fatty acid oxidation, suggesting potential roles in peroxisomal ␤-oxidation. We investigated ACH2 to determine whether it has a similar role in the plant cell. Like its eukaryotic homologs, ACH2 carries a putative type 1 peroxisomal targeting sequence (-SKL COOH ), and maintains all the catalytic residues typical of this family of acyl-CoA thioesterases. Analytical ultracentrifugation of recombinant ACH2-6His shows that it associates as a 196-kDa homotetramer in vitro, a result that is significant in light of the cooperative kinetics demonstrated by ACH2-6His in vitro. The cooperative effects are most pronounced with medium chain acyl-CoAs, where the Hill coefficient is 3.8 for lauroyl-CoA, but decrease for long chain acyl-CoAs, where the Hill coefficient is only 1.9 for oleoyl-CoA. ACH2-6His hydrolyzes both medium and long chain fatty acyl-CoAs but has highest activity toward the long chain unsaturated fatty acyl-CoAs. Maximum rates were found with palmitoleoyl-CoA, which is hydrolyzed at 21 mol/min/mg protein. Additionally, ACH2-6His is insensitive to feedback inhibition by free CoASH levels as high as 100 M. ACH2 is most highly expressed in mature tissues such as young leaves and flowers rather than in germinating seedlings where ␤-oxidation is rapidly proceeding. Taken together, these results suggest that ACH2 activity is not linked to fatty acid oxidation as has been suggested for its eukaryotic homologs, but rather has a unique role in the plant cell.

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“…Other upregulated genes involved in fatty acid metabolism which are known to respond to PPAR␣ activators include carnitine O-octanoyltransferase (Crot) (9), cytosolic acyl-CoA thioesterase 1 (Cte1) (70), and the microsomal cytochrome P450 4A3 (Cyp4a3) that catalyzes -hydroxylation of fatty acids (32). Genes for peroxisomal and mitochondrial enzymes involved in ␤-oxidation are known to be regulated by PPAR␣, and PPRE sequences have been identified in the promoters of many of them such as Acoa1 (49,66) and Cte1 (70).…”

Section: Rnas Ten Different Control Rnas (C1-c10)mentioning

confidence: 99%

Liver gene expression in rats in response to the peroxisome proliferator-activated receptor-α agonist ciprofibrate

Yadetie

Lægreid

Bakke

et al. 2003

Physiological Genomics

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Fibrate class hypolipidemic drugs such as ciprofibrate activate the peroxisome proliferator-activated receptor-α (PPARα), which is involved in processes including lipid metabolism and hepatocyte proliferation in rodents. We examined the effects of ciprofibrate (50 mg/kg body wt per day for 60 days) on liver gene expression in rats using cDNA microarrays. The 60-day dosing period was chosen to elucidate both the metabolic and proliferative actions of this substance, while avoiding confounding effects from the hepatic carcinogenesis seen during more long-term stimulation. Ciprofibrate changed the expression of many genes including previously known PPARα agonist-responsive genes involved in processes such as lipid metabolism and inflammatory responses. In addition, many novel candidate genes involved in sugar metabolism, transcription, signal transduction, cell proliferation, and stress responses appeared to be differentially regulated in ciprofibrate-dosed rats. Ciprofibrate also resulted in significant increases in liver weight and hepatocyte proliferation. The cDNA microarray results were confirmed by Northern blot analysis for selected genes. This study thus identifies many genes that appear to be differentially regulated in ciprofibrate-dosed rats, and some of these are potential targets of PPARα. The functional diversity of these candidate genes suggests that most of them are likely to be differentially regulated as indirect consequence of the many processes affected by ciprofibrate in rodent liver. Although caution is advisable in the interpretation of genome-wide expression data, the genes identified in the present study provide candidates for further studies that may give new insight into the mechanisms of action of peroxisome proliferators.

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cDNA Cloning and Genomic Organization of Peroxisome Proliferator-Inducible Long-Chain Acyl-CoA Hydrolase from Rat Liver Cytosol

Cited by 20 publications

References 30 publications

The acyl-CoA thioesterase I is regulated by PPARα and HNF4α via a distal response element in the promoter

The acyl-CoA thioesterase I is regulated by PPARα and HNF4α via a distal response element in the promoter

Biochemical and Molecular Characterization of ACH2, an Acyl-CoA Thioesterase from Arabidopsis thaliana

Liver gene expression in rats in response to the peroxisome proliferator-activated receptor-α agonist ciprofibrate

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