論文 - 詳細
| RRC ID | 67457 |
|---|---|
| 著者 | Hitomi K, Okada R, Loo TM, Miyata K, Nakamura AJ, Takahashi A. |
| タイトル | DNA Damage Regulates Senescence-Associated Extracellular Vesicle Release via the Ceramide Pathway to Prevent Excessive Inflammatory Responses. |
| ジャーナル | Int J Mol Sci |
| Abstract |
DNA damage, caused by various oncogenic stresses, can induce cell death or cellular senescence as an important tumor suppressor mechanism. Senescent cells display the features of a senescence-associated secretory phenotype (SASP), secreting inflammatory proteins into surrounding tissues, and contributing to various age-related pathologies. In addition to this inflammatory protein secretion, the release of extracellular vesicles (EVs) is also upregulated in senescent cells. However, the molecular mechanism underlying this phenomenon remains unclear. Here, we show that DNA damage activates the ceramide synthetic pathway, via the downregulation of sphingomyelin synthase 2 (SMS2) and the upregulation of neutral sphingomyelinase 2 (nSMase2), leading to an increase in senescence-associated EV (SA-EV) biogenesis. The EV biogenesis pathway, together with the autophagy-mediated degradation pathway, functions to block apoptosis by removing cytoplasmic DNA fragments derived from chromosomal DNA or bacterial infections. Our data suggest that this SA-EV pathway may play a prominent role in cellular homeostasis, particularly in senescent cells. In summary, DNA damage provokes SA-EV release by activating the ceramide pathway to protect cells from excessive inflammatory responses. |
| 巻・号 | 21(10) |
| 公開日 | 2020-5-25 |
| DOI | 10.3390/ijms21103720 |
| PII | ijms21103720 |
| PMID | 32466233 |
| PMC | PMC7279173 |
| MeSH | Animals Autophagy Cell Line Cells, Cultured Cellular Senescence* Ceramides / metabolism* DNA Damage* Extracellular Vesicles / metabolism* Humans Male Mice Mice, Inbred ICR Sphingomyelin Phosphodiesterase / genetics Sphingomyelin Phosphodiesterase / metabolism Transferases (Other Substituted Phosphate Groups) / genetics Transferases (Other Substituted Phosphate Groups) / metabolism |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) |