Inhibition of troponin C production without affecting other muscle protein synthesis by the antisense oligodeoxynucleotide
The effect of blocking expression of a specific gene with antisense phosphodiester oligodeoxynucleotides on the coordinate regulation of myogenesis was studied. Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region...
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Veröffentlicht in: | Antisense & nucleic acid drug development 1997-02, Vol.7 (1), p.31-38 |
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description | The effect of blocking expression of a specific gene with antisense phosphodiester oligodeoxynucleotides on the coordinate regulation of myogenesis was studied. Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% inhibition of expression of a specific isoform of TnC was achieved. However, inhibition of the TnC expression did not appreciably alter the pattern of myogenesis of mouse C2C12 cells. The differentiated murine muscle cells were able to cope with this reduced level of the target gene expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. This oligomer was found to be ineffective in blocking TnC gene expression. |
doi_str_mv | 10.1089/oli.1.1997.7.31 |
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Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% inhibition of expression of a specific isoform of TnC was achieved. However, inhibition of the TnC expression did not appreciably alter the pattern of myogenesis of mouse C2C12 cells. The differentiated murine muscle cells were able to cope with this reduced level of the target gene expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. 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Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% inhibition of expression of a specific isoform of TnC was achieved. However, inhibition of the TnC expression did not appreciably alter the pattern of myogenesis of mouse C2C12 cells. The differentiated murine muscle cells were able to cope with this reduced level of the target gene expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. This oligomer was found to be ineffective in blocking TnC gene expression.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - genetics</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Muscle Proteins - biosynthesis</subject><subject>Muscle Proteins - drug effects</subject><subject>Muscle, Skeletal - cytology</subject><subject>Oligonucleotides, Antisense - genetics</subject><subject>Oligonucleotides, Antisense - metabolism</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Peptides - drug effects</subject><subject>Protein Synthesis Inhibitors - pharmacology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - chemistry</subject><subject>RNA, Messenger - drug effects</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Thionucleotides - metabolism</subject><subject>Thionucleotides - pharmacology</subject><subject>Troponin C - antagonists & inhibitors</subject><subject>Troponin C - biosynthesis</subject><subject>Troponin C - genetics</subject><subject>Troponin C - metabolism</subject><issn>1087-2906</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTlPAzEQhV2AQgjUVEiu6LLxsWeJIo5IkWigtrz2ODHa2GHtFYRfj5dEtFS23nxvNDMPoRtKMkrqZuE7m9GMNk2VVRmnZ2ia5GrOGlJeoMsQ3gmhrC74BE0aUhSEl1P0vXJb29povcPe4Nj7vXfW4SXe914P6rfwaePWDxFLYyApboN93EKPd0NQHYxkhOQJB5fkYANuDzj9sHTRBnABcBpt4zX4r4MbksVHq-EKnRvZBbg-vTP09vjwunyer1-eVsv79VxxxuO8yEExA5QYJqFlps1LxjhjUCma1yDbSlWs5BpkqYqiUDLXkOe1blpZG61rPkN3x75pzo8BQhQ7GxR0nXTghyCqui4bRvi_IC1Jns43gosjqHofQg9G7Hu7k_1BUCLGKETaV1AxRiEqwWly3J5aD-0O9B9_yoH_AH0ui8I</recordid><startdate>19970201</startdate><enddate>19970201</enddate><creator>Ojala, J</creator><creator>Choudhury, M</creator><creator>Bag, J</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19970201</creationdate><title>Inhibition of troponin C production without affecting other muscle protein synthesis by the antisense oligodeoxynucleotide</title><author>Ojala, J ; 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Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% inhibition of expression of a specific isoform of TnC was achieved. However, inhibition of the TnC expression did not appreciably alter the pattern of myogenesis of mouse C2C12 cells. The differentiated murine muscle cells were able to cope with this reduced level of the target gene expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. This oligomer was found to be ineffective in blocking TnC gene expression.</abstract><cop>United States</cop><pmid>9055036</pmid><doi>10.1089/oli.1.1997.7.31</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Base Sequence Cell Differentiation - drug effects Cell Differentiation - genetics Cell Line Gene Expression Regulation - drug effects Gene Expression Regulation - genetics Mice Molecular Sequence Data Muscle Proteins - biosynthesis Muscle Proteins - drug effects Muscle, Skeletal - cytology Oligonucleotides, Antisense - genetics Oligonucleotides, Antisense - metabolism Oligonucleotides, Antisense - pharmacology Peptides - drug effects Protein Synthesis Inhibitors - pharmacology RNA, Messenger - biosynthesis RNA, Messenger - chemistry RNA, Messenger - drug effects Sequence Homology, Nucleic Acid Thionucleotides - metabolism Thionucleotides - pharmacology Troponin C - antagonists & inhibitors Troponin C - biosynthesis Troponin C - genetics Troponin C - metabolism |
title | Inhibition of troponin C production without affecting other muscle protein synthesis by the antisense oligodeoxynucleotide |
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