Mycoplasma fermentans inhibits the activity of cellular DNA topoisomerase I by activation of PARP1 and alters the efficacy of its anti-cancer inhibitor
| Autor: | Shulamith Horowitz, Esther Priel, Reuven Afriat |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Bacterial Diseases
Poly Adenosine Diphosphate Ribose Mycoplasma Pneumonia Poly (ADP-Ribose) Polymerase-1 Gene Expression lcsh:Medicine Biochemistry PARP1 Gene expression Molecular Cell Biology Breast Tumors lcsh:Science Neurological Tumors Mycoplasma fermentans Multidisciplinary biology Obstetrics and Gynecology MAP Kinase Kinase Kinases Enzymes Infectious Diseases DNA Topoisomerases Type I Oncology Medical Microbiology Benzamides Host-Pathogen Interactions MCF-7 Cells Medicine Poly(ADP-ribose) Polymerases medicine.drug Research Article MAP Kinase Signaling System Poly ADP ribose polymerase Topoisomerase-I Inhibitor Poly(ADP-ribose) Polymerase Inhibitors Microbiology Enzyme Regulation Enzyme activator Bacterial Proteins DNA-binding proteins Breast Cancer medicine Humans Mycoplasma Infections Protein Kinase Inhibitors Biology Topoisomerase lcsh:R Proteins Cancers and Neoplasms DNA biology.organism_classification Molecular biology Enzyme Activation Drug Resistance Neoplasm biology.protein Camptothecin lcsh:Q Topoisomerase I Inhibitors Glioblastoma Multiforme |
| Zdroj: | PLoS ONE, Vol 8, Iss 8, p e72377 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | To understand the effects of the interaction between Mycoplasma and cells on the host cellular function, it is important to elucidate the influences of infection of cells with Mycoplasma on nuclear enzymes such as DNA Topoisomerase type I (Topo I). Human Topo I participates in DNA transaction processes and is the target of anti-cancer drugs, the camptothecins (CPTs). Here we investigated the mechanism by which infection of human tumor cells with Mycoplasma fermentans affects the activity and expression of cellular Topo I, and the anti-cancer efficacy of CPT. Human cancer cells were infected or treated with live or sonicated M. fermentans and the activity and expression of Topo I was determined. M. fermentans significantly reduced (by 80%) Topo I activity in the infected/treated tumor cells without affecting the level of Topo I protein. We demonstrate that this reduction in enzyme activity resulted from ADP-ribosylation of the Topo I protein by Poly-ADP-ribose polymerase (PARP-1). In addition, pERK was activated as a result of the induction of the MAPK signal transduction pathway by M. fermentans. Since PARP-1 was shown to be activated by pERK, we concluded that M. fermentans modified the cellular Topo I activity by activation of PARP-I via the induction of the MAPK signal transduction pathway. Moreover, the infection of tumor cells with M. fermentans diminished the inhibitory effect of CPT. The results of this study suggest that modification of Topo I activity by M. fermentans may alter cellular gene expression and the response of tumor cells to Topo I inhibitors, influencing the anti-cancer capacity of Topo I antagonists. |
| Databáze: | OpenAIRE |
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