Reactive oxygen species-mediated senescence is accelerated by inhibiting Cdk2 in Idh2-deficient conditions
| Autor: | Unbin Chae, Sang-Rae Lee, Dong-Seok Lee, Hyun-Shik Lee, Hong Jun Lee, Jeen-Woo Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Senescence
Cyclin-Dependent Kinase Inhibitor p21 Aging Cell cycle checkpoint senescence reactive oxygen species (ROS) IDH2 Mice Animals cyclin-dependent kinase 2 (Cdk2) Cellular Senescence chemistry.chemical_classification Mice Knockout Reactive oxygen species biology Kinase Cyclin-dependent kinase 2 Cyclin-Dependent Kinase 2 Cell Biology Cell cycle Fibroblasts Embryo Mammalian Isocitrate Dehydrogenase Cell biology Citric acid cycle chemistry biology.protein NIH 3T3 Cells cell cycle isocitrate dehydrogenase 2 (IDH2) Reactive Oxygen Species Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Among the many factors that promote cellular senescence, reactive oxygen species (ROS) are a focus of intense research because of their critical role in accelerating cellular senescence and initiating senescence-related diseases that can be fatal. Therefore, maintaining the proper balance of ROS in cells is a key method to alleviate senescence. Recent studies have found that isocitrate dehydrogenase 2 (IDH2), a critical enzyme of the tricarboxylic acid cycle, participates in ROS generation and in cellular dysfunction that is induced by excessive levels of ROS. Loss of IDH2 induces mitochondrial dysfunction that promotes excessive ROS generation and the development of several diseases. The results of this study suggest that Idh2 plays an important role in cellular senescence. Idh2 deficiency resulted in senescence-associated phenotypes and increased levels of senescence marker proteins in mouse embryonic fibroblasts and tissues. Furthermore, excessive ROS were generated in Idh2-deficient conditions, promoting cellular senescence by inducing cell cycle arrest through cyclin-dependent kinase 2. These results indicate that loss of Idh2 is a critical factor in regulating cellular senescence. Taken together, our findings contribute to the field of senescence research and suggest that IDH2 is a potential target of future anti-senescence studies. |
| Databáze: | OpenAIRE |
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