Sp1 as a target site for metal-induced perturbations of transcriptional regulation of developmental brain gene expression

Zawia, Nasser H.; Sharan, R; Brydie, M; Oyama, Tohru; Crumpton, T.L.

doi:10.1016/s0165-3806(98)00023-6

Cited by 114 publications

(96 citation statements)

References 36 publications

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“…In each exposure scenario, 200 ppm Pb-acetate (Sigma, St. Louis, MO) was added to the deionized drinking water of the dams or the aging animals. We found that tissue Pb levels were comparatively low at this dose, and no gross morphological or nutritional disturbances were found in the pups or the aging animals (Zawia et al, 1998;Basha et al, 2003). Food and water were freely available for all the groups throughout the study.…”

Section: Methodsmentioning

confidence: 88%

“…The final suspensions were centrifuged at 12,000 ϫ g for 10 min at 4°C. The supernatants were transferred to 1.5 ml tubes, snap frozen in an ethanol dry-ice bath, and then stored at Ϫ80°C (Zawia et al, 1998;Basha et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

“…The gel was dried and exposed to a phosphor screen for 2 h and scanned in the Typhoon Variable Mode Imager 9410. The resulting scanned gels were analyzed for shifted bands and quantitated using the Image Quant 5.0 software (Zawia et al, 1998;Basha et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

“…The final PCR product was analyzed onto a 1% agarose/ethidium bromide gel by running the gel at 80 V in 0.5ϫ Tris-borate EDTA buffer for ϳ90 min and scanned in the Typhoon Variable Mode Imager 9410. The resulting scanned gels were quantitated and analyzed using the Image Quant 5.0 software (Zawia et al, 1998;Basha et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

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The Fetal Basis of Amyloidogenesis: Exposure to Lead and Latent Overexpression of Amyloid Precursor Protein and β-Amyloid in the Aging Brain

Basha¹,

Wei²,

Bakheet³

et al. 2005

J. Neurosci.

331

239

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The fetal basis of adult disease (FeBAD) hypothesis states that many adult diseases have a fetal origin. According to FeBAD, injury or environmental influences occurring at critical periods of organ development could result in "programmatic" changes via alterations in gene expression or gene imprinting that may result in functional deficits that become apparent later in life. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by excessive deposits of aggregated ␤-amyloid (A␤) peptides, which are snippets of the ␤-amyloid precursor protein (APP). The predominately sporadic nature of AD suggests that the environment must play a role in neurodegeneration. To examine latent responses to an environmental agent, we exposed rodents to lead and monitored the lifetime expression of the APP gene. We observed that APP mRNA expression was transiently induced in neonates, but exhibited a delayed overexpression 20 months after exposure to Pb had ceased. This upregulation in APP mRNA expression was commensurate with a rise in activity of the transcription factor Sp1, one of the regulators of the APP gene. Furthermore, the increase in APP gene expression in old age was accompanied by an elevation in APP and its amyloidogenic A␤ product. In contrast, APP expression, Sp1 activity, as well as APP and A␤ protein levels were unresponsive to Pb exposure during old age. These data suggested that environmental influences occurring during brain development predetermined the expression and regulation of APP later in life, potentially altering the course of amyloidogenesis.

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Section: Methodsmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The Fetal Basis of Amyloidogenesis: Exposure to Lead and Latent Overexpression of Amyloid Precursor Protein and β-Amyloid in the Aging Brain

Basha¹,

Wei²,

Bakheet³

et al. 2005

J. Neurosci.

331

239

View full text Add to dashboard Cite

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“…These results indicate that Ets-1 can bind to and trans-activate the DOR promoter in the neonatal mouse brain. Interestingly, the expression of the DOR gene is rarely detected in the mouse brain throughout the prenatal development, although Ets-1, USF, and the Sp family proteins are present in the prenatal mouse brain (5,33,45,51). This phenomenon suggests that other uncovered factors or regulation mechanisms that appear during the neonatal development are also required for the rapid development of the DOR system in the neonatal mouse brain.…”

Section: Ets-1 Trans-activates Mouse ␦-Opioid Receptor Gene Promotermentioning

confidence: 99%

Transcriptional Regulation of Mouse δ-Opioid Receptor Gene

Sun

Loh

2001

Journal of Biological Chemistry

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Previously, we identified a minimum core promoter of the mouse ␦-opioid receptor (DOR) gene. The DOR promoter contains an E-box that binds upstream stimulatory factor and is crucial for the DOR promoter activity in NS20Y cells, a mouse neuronal cell line that constitutively expresses DOR. In the present study, we further analyzed the DOR promoter in NS20Y cells and have demonstrated that transcription factor Ets-1 binds to an Ets-1-binding site overlapping the E-box and trans-activates the DOR promoter by synergizing with upstream stimulatory factor in specific DNA binding. In addition, the Ets-1 DNA-binding domain is sufficient to play the functional role of Ets-1 in trans-activating the DOR promoter. Furthermore, through in vivo cross-linking assays and Northern blot analyses, we have demonstrated that Ets-1 binds to the DOR promoter in the neonatal mouse brain and that overexpressed Ets-1 can significantly enhance the expression of DOR mRNA in primary neonatal mouse neuronal cells. Collectively, our data suggest that Ets-1 functions as a trans-activator of the DOR promoter in the neonatal mouse brain and thus may contribute to the development of the mouse brain DOR system.Opioids are the preferred clinical analgesics for severe pain. Three major types of opioid receptors (ORs), 1 , ␦, and , have been cloned and shown to belong to the G protein-coupled receptor superfamily (1). Although all three ORs mediate opioid-induced analgesia, each receptor type exhibits a distinct pharmacological profile as well as a unique pattern of temporal and spatial expression (2-3).The localization of the ␦-opioid receptor (DOR) generally matches the pharmacological action sites of ␦-opioids (2). In addition, it has been reported that the expression levels of DOR can determine the DOR agonist's activities (4). Thus, understanding the molecular mechanism underlying the spatiotemporal expression of DOR may raise the possibility of maximizing the pharmacological benefits of ␦-opioids by manipulation of the DOR expression levels.DOR is mainly confined to the central nervous system. There is a strong correlation between the spatiotemporal presence of DOR mRNA and ␦-opioid-binding sites (5). In addition, levels of DOR mRNA as well as ␦-opioid-binding sites can be regulated by various agents in some neuronal cell lines. For example, nerve growth factor (6), ethanol (7), or retinoic acid (8) can up-regulate DOR mRNA and ␦-opioid-binding sites. On the other hand, activation of the protein kinase A pathway by forskolin or cyclic AMP analogues results in down-regulation of DOR mRNA and ␦-opioid-binding sites (9). All of these studies suggest that the expression of DOR is subjected to several regulation mechanisms at the transcriptional level. Therefore, study of the transcriptional regulation of DOR gene will provide insights into the spatiotemporal expression of DOR.Previously, we identified a minimum core promoter of the mouse DOR gene. We found that an E box and a GC box in the DOR promoter are crucial for the DOR promoter activity in N...

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Determining the Ability of Xenobiotic Metals to Bind a Specific Protein Domain by Electrophoresis

2003

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Environmental metals are potentially toxic and can interfere with the metal-binding motifs of various critical proteins. This unit describes an electrophoretic method that can be used to measure the ability of a xenobiotic metal to bind a zinc-finger motif. Information gained using this protocol can lead to the identification of protein targets of metals and shed better light on their mechanisms of action.

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Sp1 as a target site for metal-induced perturbations of transcriptional regulation of developmental brain gene expression

Cited by 114 publications

References 36 publications

The Fetal Basis of Amyloidogenesis: Exposure to Lead and Latent Overexpression of Amyloid Precursor Protein and β-Amyloid in the Aging Brain

The Fetal Basis of Amyloidogenesis: Exposure to Lead and Latent Overexpression of Amyloid Precursor Protein and β-Amyloid in the Aging Brain

Transcriptional Regulation of Mouse δ-Opioid Receptor Gene

Determining the Ability of Xenobiotic Metals to Bind a Specific Protein Domain by Electrophoresis

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