Identification of a novel compound that inhibits both mitochondria-mediated necrosis and apoptosis
| Autor: | Issei Komuro, Hiroshi Akazawa, Ikuko Nakanomyo, Shigeomi Shimizu, Yoko Kudo-Sakamoto, Satoko Arakawa |
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| Rok vydání: | 2015 |
| Předmět: |
Mice
Knockout Programmed cell death Necrosis Transition (genetics) Biophysics Apoptosis Cell Biology Biology Mitochondrion Biochemistry Embryonic stem cell Mitochondria Cell biology Chemical library Mice chemistry.chemical_compound chemistry medicine Animals medicine.symptom Inner mitochondrial membrane Molecular Biology |
| Zdroj: | Biochemical and Biophysical Research Communications. 467:1006-1011 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.10.022 |
| Popis: | In various pathological events, particularly in oxygen radical-mediated cell injury, both apoptosis and necrosis play essential roles. Apoptosis and some types of necrosis are induced via increases in mitochondrial membrane permeability, called mitochondrial outer membrane permeabilization (MOMP) and permeability transition pore (PTP) opening, respectively. To search for small compounds that inhibit both MOMP-mediated apoptosis and PTP-mediated necrosis, we performed a mitochondria-based high-throughput screening of a chemical library. We identified TMD#7538, a small compound that inhibits both MOMP and PTP opening. Consistent with the fact that this compound inhibited both apoptosis and necrosis, it efficiently suppressed H2O2-induced cell death in mouse embryonic fibroblasts and rat neonatal cardiomyocytes. |
| Databáze: | OpenAIRE |
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