The Same Xenobiotic Response Element Is Required for Constitutive and Inducible Expression of the Mammalian Aldehyde Dehydrogenase-3 Gene

Boesch, Josette S.; Miskimins, Robin; Miskimins, W. Keith; Lindahl, Ronald

doi:10.1006/abbi.1998.0989

Cited by 18 publications

(18 citation statements)

References 19 publications

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“…Possibly, the poor detection of ARNT1 and AhR was due to impaired antibody species specificity. ARNT1 has been detected by others in the corneas of rats, although AhR was not (6). Although our immunoblotting gave variable quantitative results, amplicons of Arnt1, AhR, Hif-1␣, Hif-3␣, Stra13, and Hif-3␣ IPAS were obtained by RT-PCR and sequenced from rabbit corneal RNA, indicating expression of these genes in the cornea (data not shown).…”

Section: Figsupporting

confidence: 50%

“…Of particular interest are three putative XREs (Ϫ714 to Ϫ709, Ϫ3274 to Ϫ3268, Ϫ5098 to Ϫ5093) in the rabbit Aldh1a1 genomic fragment, which are not found in the upstream region of the human ALDH1A1 gene. These XREs are of interest because an XRE has been implicated in corneal expression of the rat Aldh3a1 gene (6). The XREs of mouse Aldh3a1 are responsible for its dioxin-inducible expression (43).…”

Section: Figmentioning

confidence: 99%

“…In addition, stimulated by retinoic acid protein 13 (STRA13) is another repressor protein that is induced by hypoxia but which acts through E-boxes (of sequence 5Ј-CACGT G-3Ј) rather than HREs (61). An upstream xenobiotic response element (XRE) (5Ј-TNGCGTG-3Ј) (23) associated with rat Aldh3a1 that appears necessary to drive expression of the chloramphenicol acetyltransferase reporter gene in transfected rat corneal epithelial cells (6) further implicates hypoxia or other environmental stresses in the high level of expression of corneal genes. In this connection, some of the lens and cornea enzyme crystallins are genes known to be induced by hypoxia or xenobiotics in other tissues.…”

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Preferential Transcription of Rabbit Aldh1a1 in the Cornea: Implication of Hypoxia-Related Pathways

Hough

Piatigorsky

2004

Molecular and Cellular Biology

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Here we examine the molecular basis for the known preferential expression of rabbit aldehyde dehydrogenase class 1 (ALDH1A1) in the cornea. The rabbit Aldh1a1 promoter-firefly luciferase reporter transgene (؊3519 to ؉43) was expressed preferentially in corneal cells in transfection tests and in transgenic mice, with an expression pattern resembling that of rabbit Aldh1a1. The 5 flanking region of the rabbit Aldh1a1 gene resembled that in the human gene (60.2%) more closely than that in the mouse (46%) or rat (51.5%) genes. We detected three xenobiotic response elements (XREs) and one E-box consensus sequence in the rabbit Aldh1a1 upstream region; these elements are prevalent in other highly expressed corneal genes and can mediate stimulation by dioxin and repression by CoCl 2 , which simulates hypoxia. The rabbit Aldh1a1 promoter was stimulated fourfold by dioxin in human hepatoma cells and repressed threefold by CoCl 2 treatment in rabbit corneal stromal and epithelial cells. Cotransfection, mutagenesis, and gel retardation experiments implicated the hypoxia-inducible factor 3␣/aryl hydrocarbon nuclear translocator heterodimer for Aldh1a1 promoter activation via the XREs and stimulated by retinoic acid protein 13 for promoter repression via the E-box. These experiments suggest that XREs, E-boxes, and PAS domain/basic helix-loop-helix transcription factors (bHLH-PAS) contribute to preferential rabbit Aldh1a1 promoter activity in the cornea, implicating hypoxia-related pathways.Most mammalian corneas accumulate (5 to 40% depending on species) aldehyde dehydrogenase 3 (ALDH3A1) (unified nomenclature for the ALDH gene family [http://www.uchsc .edu/sp/sp/alcdbase/alcdbase.html]) mostly, but not exclusively, in their epithelium (47). While the function of the abundant ALDH3A1 in mammalian corneal epithelial cells is not established, detoxification of lipid peroxide radicals induced by UV light (26), absorption of UV (1), and a suspected structural role (47) are among the suggested possibilities. The fact that elimination of mouse ALDH3A1 (50% of corneal water-soluble protein) by homologous recombination in mice fails to show a corneal phenotype has increased the mystery of its function (44). Deficiencies in ALDH have also been implicated in keratoconus, which affects the corneal epithelium (18).Rabbits are exceptional in that they accumulate ALDH1A1 rather than ALDH3A1 in the cornea (29). ALDH1A1 comprises about 3% and ALDH3A1 comprises about 5% of the total soluble protein in human cornea (31). In contrast to the situation with ALDH3A1 in other mammals, rabbit ALDH1A1 is more abundant in the stromal cells of the cornea than in the epithelium. Wound healing experiments after freeze-induced injury suggested that the prevalence of ALDH1A1 may contribute to transparency of rabbit stromal cells (29), analogous to the role of crystallins in the lens. Indeed, -crystallin (ALDH1A8) is a lens crystallin, comprising 25% of the watersoluble protein of the elephant shrew lens (20). A protein equally similar to ALDH1A1 and ALDH2...

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confidence: 99%

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Preferential Transcription of Rabbit Aldh1a1 in the Cornea: Implication of Hypoxia-Related Pathways

Hough

Piatigorsky

2004

Molecular and Cellular Biology

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“…To our knowledge, only a limited number of functional AhR-binding sites have been identified, mostly within the promoter regions of AhR-regulated genes (Sun et al, 2004;Tijet et al, 2006), including Cyp1A1 (Cytochrome P450, 1A1) (Denison et al, 1988;Lusska et al, 1993), Cyp1A2 (Cytochrome P450, 1A2) (Quattrochi et al, 1998;Sogawa et al, 2004), Cyp1B1 (Cytochrome P450, 1B1) (Eltom et al, 1999), Nqo1 (NAD(P)H: quinone oxidoreductase 1) (Favreau and Pickett, 1991), Ugt1A1 (UDPglucuronosyltransferase 1A1) (Emi et al, 1996), Gsta1 (Glutathione S-transferase Ya) (Pimental et al, 1993), Aldh3A1 (Aldehyde dehydrogenase 3A1) (Boesch et al, 1999), Nrf2 (NF-E2 p45-related factor) (Miao et al, 2005), Pon1 (Paraoxonase 1) (Gouedard et al, 2004), Cyp19A1 (P450 aromatase) (Baba et al, 2005), c-myc (Yang et al, 2005), Cyp2S1 (Cytochrome P450, 2S1) (Rivera et al, 2007), and Cyp2A5 (Cytochrome P450, 2A5) (Arpiainen et al, 2005); Cyp1A1 and Cyp1B1 being studied most extensively as model AhR-induced genes. Previous gene expression profiling by the DNA microarray technique in mouse hepatoma Hepa-1c1c7 cells stimulated with TCDD revealed that at least 285 genes exhibited obvious changes in their expression (Dere et al, 2006), but experimental genome-wide research for direct AhR-target genes has not been carried out so far.…”

Section: Introductionmentioning

confidence: 99%

High-throughput evaluation of aryl hydrocarbon receptor-binding sites selected via chromatin immunoprecipitation-based screening in Hepa-1c1c7 cells stimulated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

et al. 2008

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“…However, evidence indicates that constitutive and inducible mechanisms are fundamentally similar. For example, previous ALDH3A1 chloramphenicol acetyl transferase (CAT) reporter gene deletion analyses indicate that both modes of expression are directed by the same regulatory regions; most notably, a region near Ϫ2.0 kb that contains a functional XRE (Takimoto et al, 1994;Boesch et al, 1999). Mutagenesis of the XRE ARNT half-site confirmed that it mediates both xenobiotic-inducible and constitutive ALDH3A1 reporter gene expression (Boesch et al, 1999).…”

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Constitutive and 3-Methylcholanthrene-Induced RatALDH3A1Expression Is Mediated by Multiple Xenobiotic Response Elements

Reisdorph

Lindahl²

2006

Drug Metab Dispos

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ABSTRACT:The rat class 3 aldehyde dehydrogenase gene (ALDH3A1) is expressed constitutively or by xenobiotic induction depending on the tissue in which it occurs. Although the mechanism that mediates inducible expression has been well characterized, relatively little is known about constitutive regulatory mechanisms. Previous ALDH3A1 promoter analyses have indicated that primary regulatory regions within the ALDH3A1 5 flanking region exert similar effects on both constitutive and inducible ALDH3A1 expression. However, promoter gene analyses that served as the basis of early work were limited by the lack of sufficient 5 flanking region sequence. To gain a more complete picture of how the 5 flanking region regulates both modes of expression, we have subcloned an 8.0-kilobase (kb) fragment from the 5 flanking region of the ALDH3A1 gene and subjected it to reporter gene analyses. We found a region located between 4.8 and 7.8 kb upstream of the noncoding first exon that drives strong ALDH3A1 reporter activity. This region contains xenobiotic response element consensus sequences that mediate constitutive and inducible ALDH3A1 reporter gene expression. Using the new generation of ALDH3A1 reporter constructs, we were unable to confirm the presence of a negative regulatory region that was apparent in previous studies using a shorter fragment of the 5 flanking region. We also demonstrate that 3-methylcholanthrene induces ALDH3A1 expression above high constitutive background in corneal epithelial cells.

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The Same Xenobiotic Response Element Is Required for Constitutive and Inducible Expression of the Mammalian Aldehyde Dehydrogenase-3 Gene

Cited by 18 publications

References 19 publications

Preferential Transcription of Rabbit Aldh1a1 in the Cornea: Implication of Hypoxia-Related Pathways

Preferential Transcription of Rabbit Aldh1a1 in the Cornea: Implication of Hypoxia-Related Pathways

High-throughput evaluation of aryl hydrocarbon receptor-binding sites selected via chromatin immunoprecipitation-based screening in Hepa-1c1c7 cells stimulated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Constitutive and 3-Methylcholanthrene-Induced RatALDH3A1Expression Is Mediated by Multiple Xenobiotic Response Elements

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