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Time-resolved Proteomic Analysis of Plasma Membrane Damage-dependent Senescence
https://doi.org/10.15102/0002001092
https://doi.org/10.15102/000200109288f0b3e3-3a72-4576-84a0-34852fd6bf7d
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GrašicJanFulltext.pdf (4.3 MB)
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GrašicJanExamAbstract.pdf (64 KB)
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GrasicJanSummary.pdf (69 KB)
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| Item type | デフォルトアイテムタイプ（フル）(1) | |||||||
|---|---|---|---|---|---|---|---|---|
| PubDate | 2026-01-30 | |||||||
| Title | ||||||||
| Title | 細胞膜損傷による細胞老化の時間分解プロテオーム解析 | |||||||
| Language | ja | |||||||
| Title | ||||||||
| Title | Time-resolved Proteomic Analysis of Plasma Membrane Damage-dependent Senescence | |||||||
| Language | en | |||||||
| Creator |
Grašic, Jan
× Grašic, Jan
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| Access Rights | ||||||||
| Access Rights | open access | |||||||
| Access Rights URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| Rights | ||||||||
| Rights | © 2025 The Author. | |||||||
| Rights | ||||||||
| Rights Resource | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||
| Rights | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |||||||
| Subject | ||||||||
| Subject Scheme | Other | |||||||
| Subject | Cellular senescence and aging | |||||||
| Description | ||||||||
| Description Type | Abstract | |||||||
| Description | Cellular senescence is a state of stable cell cycle arrest that mediates several physiological and pathological processes, including wound healing, tumor suppression, and aging. We have previously shown that transient plasma membrane damage (PMD) induces premature cellular senescence in normal human fibroblasts. The plasma membrane damage-dependent senescent cells (PMD-Sen cells) exhibit the majority of the senescent cell characteristics. PMD-Sen is primarily induced via the Ca2+-p53 regulatory axis, but not via the best-studied senescence pathway, ATM/ATR-p53. However, the proteomic profile of PMD-Sen and its potential functions in vivo remain largely unknown. To address these questions, we used normal human fibroblasts to perform time-resolved mass spectrometry-based proteomic profiling using PMD-Sen cells, DNA damage response-dependent senescent cells (DDRSen cells), and replicative senescent cells (Rep-Sen cells). These analyses identified CCN1, CCN2, CDH2, NDUFAF2, and DIP2C as proteins specifically upregulated in PMD-Sen cells. Bioinformatics revealed that, after PMD, the extracellular matrix remodeling and wound healing pathways are activated. In contrast, at the late stage of senescence, DNA replication, DNA repair, RNA splicing, and chromatin organization pathways were uniformly downregulated in PMD-Sen cells, DDR-Sen cells, and Rep-Sen cells. We also identified nobiletin as a novel senolytic and senescence prevention agent. These findings will elucidate the mechanisms underlying PMD-Sen and ultimately contribute to the utilization of PMD-Sen-specific biomarkers for in vivo analyses. | |||||||
| Language | en | |||||||
| Language | ||||||||
| Language | eng | |||||||
| Resource Type | ||||||||
| Resource Type Identifier | http://purl.org/coar/resource_type/c_db06 | |||||||
| Resource Type | doctoral thesis | |||||||
| Version Type | ||||||||
| Version Type | VoR | |||||||
| Version Type Resource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| Identifier Registration | ||||||||
| Identifier Registration | 10.15102/0002001092 | |||||||
| Identifier Registration Type | JaLC | |||||||
| Dissertation Number | ||||||||
| Dissertation Number | 甲第215号 | |||||||
| Degree Name | ||||||||
| Language | en | |||||||
| Degree Name | Doctor of Philosophy | |||||||
| Date Granted | ||||||||
| Date Granted | 2025-11-30 | |||||||
| Degree Grantor | ||||||||
| Degree Grantor Name Identifier Scheme | kakenhi | |||||||
| Degree Grantor Name Identifier | 38005 | |||||||
| Language | en | |||||||
| Degree Grantor Name | Okinawa Institute of Science and Technology Graduate University | |||||||
