A Role for H2O2 and TRPM2 in the Induction of Cell Death: Studies in KGN Cells
| العنوان: | A Role for H2O2 and TRPM2 in the Induction of Cell Death: Studies in KGN Cells |
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| المؤلفون: | Lars Kunz, Theresa Buck, Konstantin Bagnjuk, Carsten Theo Hack, Doris Mayr, Artur Mayerhofer, Katja Eubler |
| المصدر: | Antioxidants Volume 8 Issue 11 Antioxidants, Vol 8, Iss 11, p 518 (2019) |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Physiology, Trolox, Granulosa cell, Clinical Biochemistry, Cell, Mitochondrion, Biochemistry, Article, 03 medical and health sciences, 0302 clinical medicine, granulosa cell tumor, medicine, TRPM2, Molecular Biology, NADPH oxidase, biology, Chemistry, lcsh:RM1-950, NOX4, Cell Biology, Cell biology, mitochondria, lcsh:Therapeutics. Pharmacology, cell death, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, ovary, calcium channel, Intracellular |
| الوصف: | Recent studies showed that KGN cells, derived from a human granulosa cell tumor (GCT), express NADPH oxidase 4 (NOX4), an important source of H2O2. Transient receptor potential melastatin 2 (TRPM2) channel is a Ca2+ permeable cation channel that can be activated by H2O2 and plays an important role in cellular functions. It is also able to promote susceptibility to cell death. We studied expression and functionality of TRPM2 in KGN cells and examined GCT tissue microarrays (TMAs) to explore in vivo relevance. We employed live cell, calcium and mitochondrial imaging, viability assays, fluorescence activated cell sorting (FACS) analysis, Western blotting and immunohistochemistry. We confirmed that KGN cells produce H2O2 and found that they express functional TRPM2. H2O2 increased intracellular Ca2+ levels and N-(p-Amylcinnamoyl)anthranilic acid (ACA), a TRPM2 inhibitor, blocked this action. H2O2 caused mitochondrial fragmentation and apoptotic cell death, which could be attenuated by a scavenger (Trolox). Immunohistochemistry showed parallel expression of NOX4 and TRPM2 in all 73 tumor samples examined. The results suggest that GCTs can be endowed with a system that may convey susceptibility to cell death. If so, induction of oxidative stress may be beneficial in GCT therapy. Our results also imply a therapeutic potential for TRPM2 as a drug target in GCTs. |
| وصف الملف: | application/pdf |
| تدمد: | 2076-3921 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8b8045c7750a78949d9d2e67f909a8b https://doi.org/10.3390/antiox8110518 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e8b8045c7750a78949d9d2e67f909a8b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20763921 |
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