Extracellular mtDNA activates NF-κB via toll-like receptor 9 and induces cell death in cardiomyocytes
| العنوان: | Extracellular mtDNA activates NF-κB via toll-like receptor 9 and induces cell death in cardiomyocytes |
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| المؤلفون: | Jarle Vaage, Ingebjørg Seljeflot, Marte Bliksøen, Kåre-Olav Stensløkken, Lars Henrik Mariero, Anton Baysa, Guro Valen, Fred Haugen, Kirsti Ytrehus, May-Kristin Torp |
| المصدر: | Basic Research in Cardiology. 111 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Programmed cell death, Mitochondrial DNA, Physiology, Immunoblotting, Myocardial Infarction, Inflammation, 030204 cardiovascular system & hematology, Biology, DNA, Mitochondrial, Polymerase Chain Reaction, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Physiology (medical), medicine, Extracellular, Animals, Humans, Myocytes, Cardiac, chemistry.chemical_classification, Reactive oxygen species, Microscopy, Confocal, Innate immune system, Cell Death, NF-kappa B, NF-κB, Embryonic stem cell, Molecular biology, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Toll-Like Receptor 9, Female, medicine.symptom, Cardiology and Cardiovascular Medicine |
| الوصف: | Acute myocardial infarction (AMI) causes sterile inflammation, which exacerbates tissue injury. Elevated levels of circulating mitochondrial DNA (mtDNA) have been associated with AMI. We hypothesized that mtDNA triggers an innate immune response via TLR9 and NF-κB activation, causing cardiomyocyte injury. Murine cardiomyocytes express TLR9 mRNA and protein and were able to internalize fluorescently labeled mouse mtDNA. Incubation of human embryonic kidney cells with serum from AMI patients containing naturally elevated levels of mtDNA induced TLR9-dependent NF-κB activity. This effect was mimicked by isolated mtDNA. mtDNA activated NF-κB in reporter mice both in vivo and in isolated cardiomyocytes. Moreover, incubation of isolated cardiomyocytes with mtDNA induced cell death after 4 and 24 h. Laser confocal microscopy showed that incubation of cardiomyocytes with mtDNA accelerated mitochondrial depolarization induced by reactive oxygen species. In contrast to mtDNA, isolated total DNA did not activate NF-κB nor induce cell death. In conclusion, mtDNA can induce TLR9-dependent NF-κB activation in reporter cells and activate NF-κB in cardiomyocytes. In cardiomyocytes, mtDNA causes mitochondrial dysfunction and death. Endogenous mtDNA in the extracellular space is a danger signal with direct detrimental effects on cardiomyocytes. |
| تدمد: | 1435-1803 0300-8428 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::79e4871bc4a6f38420233fa7747fc83e https://doi.org/10.1007/s00395-016-0553-6 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....79e4871bc4a6f38420233fa7747fc83e |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14351803 03008428 |
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