[Induction of apoptotic endonuclease EndoG with DNA-damaging agents initiates alternative splicing of telomerase catalytic subunit hTERT and inhibition of telomerase activity hTERT in human CD4+ and CD8+ T-lymphocytes]
| Autor: | Yu. A. Gladilina, E. V. Orlova, Nikolay N. Sokolov, D. V. Grishin, M. V. Pokrovskaya, D. A. Vasina, S. S. Aleksandrova, D. D. Zhdanov, V. S. Orlova |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Telomerase DNA damage Clinical Biochemistry ENDOG CD8-Positive T-Lymphocytes Biochemistry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Endonuclease chemistry.chemical_compound 0302 clinical medicine Humans Telomerase reverse transcriptase Cells Cultured Endodeoxyribonucleases biology Chemistry Alternative splicing General Medicine Cell biology Alternative Splicing 030104 developmental biology 030220 oncology & carcinogenesis RNA splicing biology.protein Molecular Medicine Cisplatin DNA DNA Damage |
| Zdroj: | Biomeditsinskaia khimiia. 63(4) |
| ISSN: | 2310-6972 |
| Popis: | Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes. All investigated DNA-damaging agents were able to induce EndoG expression. Cisplatin, a therapeutic compound, producing DNA cross-links induced the highest level of DNA damages and EndoG expression. Incubation of CD4+ and CD8+ T-cells with cisplatin caused the changes in proportion of hTERT splice variants and inhibition of telomerase activity.Aktivnost' kataliticheskoĭ sub"edinitsy telomerazy hTERT (human Telomerase Reverse Transcriptase) reguliruetsia protsessom al'ternativnogo splaĭsinga ee mRNK. V nastoiashchee vremia mekhanizm splaĭsinga hTERT izuchen nedostatochno polno. Izvestno, chto v dannom protsesse prinimaet uchastie apoptoticheskaia éndonukleaza EndoG, ékspressiia kotoroĭ indutsiruetsia v otvet na povrezhdeniia DNK. Tsel'iu raboty iavliaetsia izuchenie sposobnosti povrezhdaiushchikh DNK agentov s razlichnym mekhanizmom deĭstviia vyzyvat' induktsiiu EndoG i ingibirovat' aktivnost' telomerazy v rezul'tate aktivatsii protsessa al'ternativnogo splaĭsinga hTERT v normal'nykh aktivirovannykh CD4+ i CD8+ T-limfotsitakh cheloveka. Vse issleduemye povrezhdaiushchie DNK agenty indutsirovali EndoG. Tsisplatin, khimioterapevticheskiĭ preparat, obrazuiushchiĭ sshivki DNK, vyzyval naibol'shee kolichestvo povrezhdeniĭ DNK i naibol'shuiu induktsiiu EndoG. Inkubatsiia CD4+ i CD8+ T-kletok s tsisplatinom privodila k izmeneniiu proportsii splaĭs-variantov hTERT i ingibirovaniiu aktivnosti telomerazy. |
| Databáze: | OpenAIRE |
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