Non-sequence-specific inhibition of transferrin receptor expression in HL-60 leukemia cells by phosphorothioate oligodeoxynucleotides.
Identifieur interne : 004869 ( Main/Exploration ); précédent : 004868; suivant : 004870Non-sequence-specific inhibition of transferrin receptor expression in HL-60 leukemia cells by phosphorothioate oligodeoxynucleotides.
Auteurs : P T Ho [États-Unis] ; K. Ishiguro ; E. Wickstrom ; A C SartorelliSource :
- Antisense research and development [ 1050-5261 ] ; 1991.
Descripteurs français
- KwdFr :
- Cinétique, Division cellulaire (), Données de séquences moléculaires, Humains, Leucémie aiguë promyélocytaire, Lignée cellulaire, Oligonucléotides antisens (métabolisme), Oligonucléotides antisens (pharmacologie), Oligonucléotides antisens (synthèse chimique), Organothiophosphates (pharmacologie), Récepteurs à la transferrine (), Récepteurs à la transferrine (génétique), Récepteurs à la transferrine (métabolisme), Régulation de l'expression des gènes tumoraux (), Stabilité de médicament, Séquence nucléotidique, Transport biologique.
- MESH :
- génétique : Récepteurs à la transferrine.
- métabolisme : Oligonucléotides antisens, Récepteurs à la transferrine.
- pharmacologie : Oligonucléotides antisens, Organothiophosphates.
- synthèse chimique : Oligonucléotides antisens.
- Cinétique, Division cellulaire, Données de séquences moléculaires, Humains, Leucémie aiguë promyélocytaire, Lignée cellulaire, Récepteurs à la transferrine, Régulation de l'expression des gènes tumoraux, Stabilité de médicament, Séquence nucléotidique, Transport biologique.
English descriptors
- KwdEn :
- Base Sequence, Biological Transport, Cell Division (drug effects), Cell Line, Drug Stability, Gene Expression Regulation, Neoplastic (drug effects), Humans, Kinetics, Leukemia, Promyelocytic, Acute, Molecular Sequence Data, Oligonucleotides, Antisense (chemical synthesis), Oligonucleotides, Antisense (metabolism), Oligonucleotides, Antisense (pharmacology), Organothiophosphates (pharmacology), Receptors, Transferrin (drug effects), Receptors, Transferrin (genetics), Receptors, Transferrin (metabolism).
- MESH :
- chemical , chemical synthesis : Oligonucleotides, Antisense.
- drug effects : Cell Division, Gene Expression Regulation, Neoplastic, Receptors, Transferrin.
- chemical , genetics : Receptors, Transferrin.
- chemical , metabolism : Oligonucleotides, Antisense, Receptors, Transferrin.
- chemical , pharmacology : Oligonucleotides, Antisense, Organothiophosphates.
- Base Sequence, Biological Transport, Cell Line, Drug Stability, Humans, Kinetics, Leukemia, Promyelocytic, Acute, Molecular Sequence Data.
Abstract
A series of phosphodiester and phosphorothioate antisense oligodeoxynucleotides were synthesized against the human transferrin receptor (TfR). The phosphorothioate analogs exhibited marked biologic efficacy in culture, as assessed by inhibition of surface TfR content and HL-60 cell growth, whereas their unmodified phosphodiester counterparts were ineffective. Phosphorothioate oligodeoxynucleotides were more resistant to hydrolysis by serum and cellular nucleases and were more readily taken up by cells than phosphodiesters, thus providing a partial explanation for the differences in biologic activity. A length effect was observed, with antisense 30-mers exhibiting greater TfR inhibitory activity than 17-mers. The degree of receptor inhibition observed, however, was not sequence dependent, suggesting that the phosphorothioate oligodeoxynucleotides may have pleiotropic activities in eukaryotic cells in addition to inhibiting gene expression by classic antisense complementary binding to mRNA.
DOI: 10.1089/ard.1991.1.329
PubMed: 1821654
Affiliations:
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Le document en format XML
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Ishiguro</name></author><author><name sortKey="Wickstrom, E" sort="Wickstrom, E" uniqKey="Wickstrom E" first="E" last="Wickstrom">E. Wickstrom</name></author><author><name sortKey="Sartorelli, A C" sort="Sartorelli, A C" uniqKey="Sartorelli A" first="A C" last="Sartorelli">A C Sartorelli</name></author></analytic><series><title level="j">Antisense research and development</title><idno type="ISSN">1050-5261</idno><imprint><date when="1991" type="published">1991</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Biological Transport</term><term>Cell Division (drug effects)</term><term>Cell Line</term><term>Drug Stability</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>Humans</term><term>Kinetics</term><term>Leukemia, Promyelocytic, Acute</term><term>Molecular Sequence Data</term><term>Oligonucleotides, Antisense (chemical synthesis)</term><term>Oligonucleotides, Antisense (metabolism)</term><term>Oligonucleotides, Antisense (pharmacology)</term><term>Organothiophosphates (pharmacology)</term><term>Receptors, Transferrin (drug effects)</term><term>Receptors, Transferrin (genetics)</term><term>Receptors, Transferrin (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cinétique</term><term>Division cellulaire ()</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Leucémie aiguë promyélocytaire</term><term>Lignée cellulaire</term><term>Oligonucléotides antisens (métabolisme)</term><term>Oligonucléotides antisens (pharmacologie)</term><term>Oligonucléotides antisens (synthèse chimique)</term><term>Organothiophosphates (pharmacologie)</term><term>Récepteurs à la transferrine ()</term><term>Récepteurs à la transferrine (génétique)</term><term>Récepteurs à la transferrine (métabolisme)</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Stabilité de médicament</term><term>Séquence nucléotidique</term><term>Transport biologique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Division</term><term>Gene Expression Regulation, Neoplastic</term><term>Receptors, Transferrin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Transferrin</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Récepteurs à la transferrine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Oligonucleotides, Antisense</term><term>Receptors, Transferrin</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Oligonucléotides antisens</term><term>Récepteurs à la transferrine</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Oligonucléotides antisens</term><term>Organothiophosphates</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Oligonucleotides, Antisense</term><term>Organothiophosphates</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Biological Transport</term><term>Cell Line</term><term>Drug Stability</term><term>Humans</term><term>Kinetics</term><term>Leukemia, Promyelocytic, Acute</term><term>Molecular Sequence Data</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cinétique</term><term>Division cellulaire</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Leucémie aiguë promyélocytaire</term><term>Lignée cellulaire</term><term>Récepteurs à la transferrine</term><term>Régulation de l'expression des gènes tumoraux</term><term>Stabilité de médicament</term><term>Séquence nucléotidique</term><term>Transport biologique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A series of phosphodiester and phosphorothioate antisense oligodeoxynucleotides were synthesized against the human transferrin receptor (TfR). The phosphorothioate analogs exhibited marked biologic efficacy in culture, as assessed by inhibition of surface TfR content and HL-60 cell growth, whereas their unmodified phosphodiester counterparts were ineffective. Phosphorothioate oligodeoxynucleotides were more resistant to hydrolysis by serum and cellular nucleases and were more readily taken up by cells than phosphodiesters, thus providing a partial explanation for the differences in biologic activity. A length effect was observed, with antisense 30-mers exhibiting greater TfR inhibitory activity than 17-mers. The degree of receptor inhibition observed, however, was not sequence dependent, suggesting that the phosphorothioate oligodeoxynucleotides may have pleiotropic activities in eukaryotic cells in addition to inhibiting gene expression by classic antisense complementary binding to mRNA.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li></region></list><tree><noCountry><name sortKey="Ishiguro, K" sort="Ishiguro, K" uniqKey="Ishiguro K" first="K" last="Ishiguro">K. Ishiguro</name><name sortKey="Sartorelli, A C" sort="Sartorelli, A C" uniqKey="Sartorelli A" first="A C" last="Sartorelli">A C Sartorelli</name><name sortKey="Wickstrom, E" sort="Wickstrom, E" uniqKey="Wickstrom E" first="E" last="Wickstrom">E. Wickstrom</name></noCountry><country name="États-Unis"><region name="Connecticut"><name sortKey="Ho, P T" sort="Ho, P T" uniqKey="Ho P" first="P T" last="Ho">P T Ho</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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