DNAzyme-Mediated Silencing of Ornithine Decarboxylase†
Identifieur interne : 001A79 ( Istex/Curation ); précédent : 001A78; suivant : 001A80DNAzyme-Mediated Silencing of Ornithine Decarboxylase†
Auteurs : Joseph M. Ackermann [États-Unis] ; Sreenivas Kanugula [États-Unis] ; Anthony E. Pegg [États-Unis]Source :
- Biochemistry [ 0006-2960 ] ; 2005.
Abstract
The value of reducing the activity of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is well-appreciated. Polyamines are necessary components for cell growth, and manipulation of polyamine homeostasis may be an effective strategy for the treatment of a number of disorders, including neoplastic diseases. An approach to develop an effective DNAzyme, using the 10−23 model, against ODC is described in these studies. DNAzymes able to cleave the target ODC RNA were identified in vitro and further characterized by the effect each had on ODC protein and activity levels using in vitro translated ODC RNA. ODC protein levels and activity correlated well with the RNA cleavage activity of the DNAzyme. One of the DNAzymes, DZ IV, which exhibited good activity, was optimized for use in cell culture studies. The DNAzyme hybridization arms were altered from equal length arms varying in length (8, 9, 10, or 11 nucleotides) or to unequal length arms (7/11 nucleotides), and kinetic analyses were performed to identify the most catalytically efficient configuration. DZ IV with equal arms nine nucleotides in length proved to be the most catalytically efficient. In HEK 293 cells, DZ IV was able to reduce the amount of translated ODC protein, resulting in ∼80% reduction in ODC activitya statistically significant enhancement over the apparent antisense effect of a catalytically inactive DNAzyme. These results indicate that this DNAzyme may be a useful tool to study the function of ODC and may have potential therapeutic uses.
Url:
DOI: 10.1021/bi047918d
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001A79
Links to Exploration step
ISTEX:7DBC434DE3CDFB7FBC43A5202DCA8235BA1D9242Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>DNAzyme-Mediated Silencing of Ornithine Decarboxylase†</title>
<author><name sortKey="Ackermann, Joseph M" sort="Ackermann, Joseph M" uniqKey="Ackermann J" first="Joseph M." last="Ackermann">Joseph M. Ackermann</name>
<affiliation wicri:level="2"><mods:affiliation>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey</wicri:cityArea>
</affiliation>
<affiliation><mods:affiliation> Department of Pharmacology.</mods:affiliation>
<wicri:noCountry code="no comma"> Department of Pharmacology.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Kanugula, Sreenivas" sort="Kanugula, Sreenivas" uniqKey="Kanugula S" first="Sreenivas" last="Kanugula">Sreenivas Kanugula</name>
<affiliation wicri:level="2"><mods:affiliation>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey</wicri:cityArea>
</affiliation>
<affiliation><mods:affiliation> Department of Cellular and Molecular Physiology.</mods:affiliation>
<wicri:noCountry code="no comma"> Department of Cellular and Molecular Physiology.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pegg, Anthony E" sort="Pegg, Anthony E" uniqKey="Pegg A" first="Anthony E." last="Pegg">Anthony E. Pegg</name>
<affiliation wicri:level="2"><mods:affiliation>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey</wicri:cityArea>
</affiliation>
<affiliation><mods:affiliation> Department of Pharmacology.</mods:affiliation>
<wicri:noCountry code="no comma"> Department of Pharmacology.</wicri:noCountry>
</affiliation>
<affiliation><mods:affiliation> Department of Cellular and Molecular Physiology.</mods:affiliation>
<wicri:noCountry code="no comma"> Department of Cellular and Molecular Physiology.</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. Phone: (717) 531-8152. Fax: (717) 531-5157. E-mail: aep1@psu.edu.</mods:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:7DBC434DE3CDFB7FBC43A5202DCA8235BA1D9242</idno>
<date when="2005" year="2005">2005</date>
<idno type="doi">10.1021/bi047918d</idno>
<idno type="url">https://api.istex.fr/ark:/67375/TPS-VW6768L8-F/fulltext.pdf</idno>
<idno type="wicri:Area/Istex/Corpus">001A79</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001A79</idno>
<idno type="wicri:Area/Istex/Curation">001A79</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main">DNAzyme-Mediated Silencing of Ornithine Decarboxylase<ref type="bib" target="#bi047918dAF2">†</ref>
</title>
<author><name sortKey="Ackermann, Joseph M" sort="Ackermann, Joseph M" uniqKey="Ackermann J" first="Joseph M." last="Ackermann">Joseph M. Ackermann</name>
<affiliation wicri:level="2"><mods:affiliation>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey</wicri:cityArea>
</affiliation>
<affiliation><mods:affiliation> Department of Pharmacology.</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kanugula, Sreenivas" sort="Kanugula, Sreenivas" uniqKey="Kanugula S" first="Sreenivas" last="Kanugula">Sreenivas Kanugula</name>
<affiliation wicri:level="2"><mods:affiliation>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey</wicri:cityArea>
</affiliation>
<affiliation><mods:affiliation> Department of Cellular and Molecular Physiology.</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Pegg, Anthony E" sort="Pegg, Anthony E" uniqKey="Pegg A" first="Anthony E." last="Pegg">Anthony E. Pegg</name>
<affiliation wicri:level="2"><mods:affiliation>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Departments of Pharmacology and Cellular and Molecular Physiology, Milton S. Hershey Medical Center,Pennsylvania State University College of Medicine, Hershey</wicri:cityArea>
</affiliation>
<affiliation><mods:affiliation> Department of Pharmacology.</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation> Department of Cellular and Molecular Physiology.</mods:affiliation>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed. Phone: (717) 531-8152. Fax: (717) 531-5157. E-mail: aep1@psu.edu.</mods:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j" type="main">Biochemistry</title>
<title level="j" type="abbrev">Biochemistry</title>
<idno type="ISSN">0006-2960</idno>
<idno type="eISSN">1520-4995</idno>
<imprint><publisher>American Chemical Society</publisher>
<date type="e-published">2005</date>
<date type="published">2005</date>
<biblScope unit="vol">44</biblScope>
<biblScope unit="issue">6</biblScope>
<biblScope unit="page" from="2143">2143</biblScope>
<biblScope unit="page" to="2152">2152</biblScope>
</imprint>
<idno type="ISSN">0006-2960</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0006-2960</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract">The value of reducing the activity of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is well-appreciated. Polyamines are necessary components for cell growth, and manipulation of polyamine homeostasis may be an effective strategy for the treatment of a number of disorders, including neoplastic diseases. An approach to develop an effective DNAzyme, using the 10−23 model, against ODC is described in these studies. DNAzymes able to cleave the target ODC RNA were identified in vitro and further characterized by the effect each had on ODC protein and activity levels using in vitro translated ODC RNA. ODC protein levels and activity correlated well with the RNA cleavage activity of the DNAzyme. One of the DNAzymes, DZ IV, which exhibited good activity, was optimized for use in cell culture studies. The DNAzyme hybridization arms were altered from equal length arms varying in length (8, 9, 10, or 11 nucleotides) or to unequal length arms (7/11 nucleotides), and kinetic analyses were performed to identify the most catalytically efficient configuration. DZ IV with equal arms nine nucleotides in length proved to be the most catalytically efficient. In HEK 293 cells, DZ IV was able to reduce the amount of translated ODC protein, resulting in ∼80% reduction in ODC activitya statistically significant enhancement over the apparent antisense effect of a catalytically inactive DNAzyme. These results indicate that this DNAzyme may be a useful tool to study the function of ODC and may have potential therapeutic uses.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001A79 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 001A79 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Istex |étape= Curation |type= RBID |clé= ISTEX:7DBC434DE3CDFB7FBC43A5202DCA8235BA1D9242 |texte= DNAzyme-Mediated Silencing of Ornithine Decarboxylase† }}
This area was generated with Dilib version V0.6.33. |