Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization.

Varanasi, Usha; Chu, Ruiyin; Chu, Su; Espinosa, Rafael; LeBeau, Michelle M.; Reddy, Janardan K.

doi:10.1073/pnas.91.8.3107

Cited by 90 publications

(74 citation statements)

References 27 publications

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“…This region is highly conserved in several species with high amino-acid identity. 19,20 Alignment of amino-acid sequences from humans (hEx3a and hEx3b) and mouse (mEx3a and mEx3b) shows 87% identity between hACOX1a and mACOX1a, and 94% identity between hACOX1b and mACOX1b (Supplementary Figure S1A). This strong conservation through evolution suggests that the two isoforms may well have different physiological functions.…”

Section: Acox1: One Gene Two Splice Variants With Differential Tissumentioning

confidence: 99%

“…[19][20][21] Indeed, alternative splicing of pre-mRNA produces two mRNA sequences harboring exon 3a or exon 3b, which both code for a 54 aminoacid region located near the N terminus. This region is highly conserved in several species with high amino-acid identity.…”

Section: Acox1: One Gene Two Splice Variants With Differential Tissumentioning

confidence: 99%

“…One of these peroxisomal disorders is pseudoneonatal adrenoleukodystrophy (P-NALD), caused by ACOX1 deficiency. 18 The ACOX1 enzyme is encoded by a single gene, which generates two splice variants, including exon 3a or exon 3b, respectively, 19,20 leading to the synthesis of two protein isoforms ACOX1a or ACOX1b. 21 A single homozygous mutation in exon 3b results in the development of the P-NALD disease, 22 suggesting different substrate specificities of the two ACOX1 isoforms.…”

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confidence: 99%

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Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

Vluggens

Andreoletti

Viswakarma

et al. 2010

Laboratory Investigation

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Disruption of the peroxisomal acyl-CoA oxidase 1 (Acox1) gene in the mouse results in the development of severe microvesicular hepatic steatosis and sustained activation of peroxisome proliferator-activated receptor-a (PPARa). These mice manifest spontaneous massive peroxisome proliferation in regenerating hepatocytes and eventually develop hepatocellular carcinomas. Human ACOX1, the first and rate-limiting enzyme of the peroxisomal b-oxidation pathway, has two isoforms including ACOX1a and ACOX1b, transcribed from a single gene. As ACOX1a shows reduced activity toward palmitoyl-CoA as compared with ACOX1b, we used adenovirally driven ACOX1a and ACOX1b to investigate their efficacy in the reversal of hepatic phenotype in Acox1(À/À) mice. In this study, we show that human ACOX1b is markedly effective in reversing the ACOX1 null phenotype in the mouse. In addition, expression of human ACOX1b was found to restore the production of nervonic (24:1) acid and had a negative impact on the recruitment of coactivators to the PPARa-response unit, which suggests that nervonic acid might well be an endogenous PPARa antagonist, with nervonoyl-CoA probably being the active form of nervonic acid. In contrast, restoration of docosahexaenoic (22:6) acid level, a retinoid-X-receptor (RXRa) agonist, was dependent on the concomitant hepatic expression of both ACOX1a and ACOX1b isoforms. This is accompanied by a specific recruitment of RXRa and coactivators to the PPARa-response unit. The human ACOX1b isoform is more effective than the ACOX1a isoform in reversing the Acox1 null phenotype in the mouse. Substrate utilization differences between the two ACOX1 isoforms may explain the reason why ACOX1b is more effective in metabolizing PPARa ligands.

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Section: Acox1: One Gene Two Splice Variants With Differential Tissumentioning

confidence: 99%

Section: Acox1: One Gene Two Splice Variants With Differential Tissumentioning

confidence: 99%

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confidence: 99%

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Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

Vluggens

Andreoletti

Viswakarma

et al. 2010

Laboratory Investigation

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“…In mammals only the rat and human palmitoyl-CoA oxidase have been cloned [13,14,[22][23][24]. We have become interested in obtaining the cDNAs of the other characterized mammalian oxidases for several reasons: first, to be able to compare their primary structures and possibly to pinpoint their active sites ; second, to discover whether their carboxy terminus conforms to the known SKL peroxisomal import signal 1251 ; third, to investigate whether a peroxisome-proliferator-activated receptor responsive element [26] is present in the promoter regions of their genes.…”

Section: -121mentioning

confidence: 99%

Rat Pristanoyl‐CoA Oxidase

Vanhooren

Fransen

Béthune

et al. 1996

European Journal of Biochemistry

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The composite pristanoyl‐CoA oxidase cDNA sequence, derived from two overlapping clones from a rat liver cDNA library and a 5′‐RACE (rapid amplification of cDNA ends) PCR fragment, consisted of 2600 bases and contained an open reading frame of 2100 bases, encoding a protein of 700 amino acids with a calculated molecular mass of 78445 Da. This value is somewhat larger than the reported molecular mass of 70 kDa as determined earlier by SDS‐gel electrophoresis. The amino acid identity with rat palmitoyl‐CoA oxidase was rather low (28%) and barely higher than that with the yeast acyl‐CoA oxidases (20%), suggesting that the palmitoyl‐CoA oxidase/pristanoyl‐CoA oxidase duplication occurred early in evolution. The carboxy‐terminal tripeptide of pristanoyl‐CoA oxidase was SQL. In vitro studies with the bacterially expressed human peroxisomal‐targeting signal‐1 import receptor indicated that SQL functions as a peroxisome‐targeting signal. Northern analysis of tissues from control and clofibrate treated rats demonstrated that the pristanoyl‐CoA oxidase gene is transcribed in liver and extrahepatic tissues and that transcription is not enhanced by treatment of rats with peroxisome proliferators. No mRNA could be detected by northern analysis of human tissues, suggesting that the human pristanoyl‐CoA oxidase gene, if present, is only poorly or not transcribed.

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“…3a). Splice variants of human ACOX1 (ACOX1a and 1b) were reported to be critical regulators in the fatty acid metabolism (Varanasi et al, 1994;Baes and Van Veldhoven, 2012), indicating that these variants were essential for the lipid metabolism in goats. Interestingly, both the ACOX1 and ACOX1-SV1 variants were expressed spaciously and differently in the collected tissue samples.…”

Section: Discussionmentioning

confidence: 99%

Novel alternative splicing variants of <i>ACOX1</i> and their differential expression patterns in goats

Liu

ChengFang

et al. 2018

Arch. Anim. Breed.

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Abstract.As the first and rate-limiting enzyme of the peroxisomal β-oxidation pathway, acyl-coenzyme A oxidase 1 (ACOX1), which is regulated by peroxisome proliferator-activated alfa (PPARα), is vital for fatty acid oxidation and deposition, especially in the lipid metabolism of very long-chain fatty acids. Alternative splicing events of ACOX1 have been detected in rodents, Nile tilapia, zebra fish and humans but not in goats. Herein, we identified a novel splice variant of the ACOX1 gene, which was designated as ACOX1-SV1, in addition to the complete transcript, ACOX1, in goats. The length of the ACOX1-SV1 coding sequence was 1983 bp, which presented a novel exon 2 variation owing to alternative 5 -splice site selection in exon 2 and partial intron 1, compared to that in ACOX1. The protein sequence analysis indicated that ACOX1-SV1 was conserved across different species. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis showed that these two isoforms were expressed spatially and differently in different tissue types. ACOX1 and ACOX1-SV1 were expressed at high levels in liver, spleen, brain and adipose tissue in kid goats, and they were abundantly expressed in the fat, liver and spleen of adults. Interestingly, whether in kids or in adults, in fat, the mRNA level of ACOX1 was considerably higher than that of ACOX1-SV1. In contrast, in the liver, the expression of ACOX1-SV1 was considerably higher than that of ACOX1. This differential expression patterns showed the existence of a tissue-dependent splice regulation. These novel findings for ACOX1 should provide new insights for further studies on the function of ACOX1 and its variants that should aid in the breeding of goats with improved meat quality.

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Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization.

Cited by 90 publications

References 27 publications

Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

Rat Pristanoyl‐CoA Oxidase

Novel alternative splicing variants of <i>ACOX1</i> and their differential expression patterns in goats

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Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization.

Cited by 90 publications

References 27 publications

Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

Functional significance of the two ACOX1 isoforms and their crosstalks with PPARα and RXRα

Rat Pristanoyl‐CoA Oxidase

Novel alternative splicing variants of &lt;i&gt;ACOX1&lt;/i&gt; and their differential expression patterns in goats

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Novel alternative splicing variants of <i>ACOX1</i> and their differential expression patterns in goats