Necroptosis occurs in osteoblasts during tumor necrosis factor-α stimulation and caspase-8 inhibition
| العنوان: | Necroptosis occurs in osteoblasts during tumor necrosis factor-α stimulation and caspase-8 inhibition |
|---|---|
| المؤلفون: | Guan Shi, Li Bao, Hao Chen, Fei Feng, Hai Tang, Pu Jia |
| المصدر: | Brazilian Journal of Medical and Biological Research, Volume: 52, Issue: 1, Article number: e7844, Published: 23 NOV 2018 Brazilian Journal of Medical and Biological Research v.52 n.1 2019 Brazilian Journal of Medical and Biological Research Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC Brazilian Journal of Medical and Biological Research, Vol 52, Iss 1 (2018) |
| بيانات النشر: | Associação Brasileira de Divulgação Científica, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Indoles, Physiology, Cell Survival, Necroptosis, Immunology, Biophysics, Ocean Engineering, Caspase 3, Inhibitor of apoptosis, Caspase 8, Biochemistry, 03 medical and health sciences, Mice, Necrosis, 0302 clinical medicine, Animals, Viability assay, General Pharmacology, Toxicology and Pharmaceutics, Phosphorylation, lcsh:QH301-705.5, lcsh:R5-920, Osteoblasts, L-Lactate Dehydrogenase, Cell growth, Chemistry, Tumor Necrosis Factor-alpha, General Neuroscience, Imidazoles, Cell Biology, General Medicine, Molecular biology, Caspase Inhibitors, Mouse osteoblast, 030104 developmental biology, lcsh:Biology (General), Apoptosis, 030220 oncology & carcinogenesis, TNF-α, Necrostatin-1, lcsh:Medicine (General), Z-IETD-FMK, Oligopeptides, Research Article |
| الوصف: | Necroptosis is a regulated cell death mechanism. However, it is unknown whether necroptosis is involved in the death of tumor necrosis factor-α (TNF-α)-treated osteoblasts. Therefore, we conducted the study with TNF-α, Nec-1 (a specific inhibitor of necroptosis), and Z-IETD-FMK (a specific inhibitor of apoptosis) to determine whether necroptosis plays a role in the death of TNF-α-treated osteoblast cell line MC3T3-E1. Cell viability, cell death, and lactate dehydrogenase (LDH) release were assayed to evaluate cytotoxicity. Specific marker proteins receptor interacting protein kinase (RIPK3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) for necroptosis, and cleaved caspase 3 for apoptosis were detected by western blot, and mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). We found that TNF-α inhibited cell proliferation in a dose- and time-dependent manner. Nec-1 plus Z-IETD-FMK restored cell viability and significantly decreased LDH release. In addition, TNF-α alone increased the cell population of AV+PI-, while Z-IETD-FMK caused a shift in the cell population from AV+PI- to AV+PI+. Furthermore, TNF-α significantly increased protein cleaved caspase 3. TNF-α plus Z-IETD-FMK significantly increased the proteins RIPK3 and MLKL phosphorylation in MC3T3-E1 cells, while the changes in mRNA levels of RIPK3, MLKL, and caspase 3 were not consistent with the changes in the corresponding protein expression levels. In conclusion, TNF-α induced preferentially apoptosis in osteoblast cell line and necroptosis played a decisive role when TNF-α-induced death was inhibited by the inhibitor of apoptosis. Combined treatment with Nec-1 and Z-IETD-FMK protected mouse osteoblasts from death induced by TNF-α. |
| وصف الملف: | text/html |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d518889ef49097246aca74c8f18874cTest http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000100603&lng=en&tlng=enTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0d518889ef49097246aca74c8f18874c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |