期刊
ANALYTICAL CHEMISTRY
卷 93, 期 5, 页码 3052-3060出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c05447
关键词
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资金
- Spanish Government [RTI2018-100910-B-C41]
- Generalitat Valenciana [2018/024]
- Spanish Ministry of Economy [FPU15/02707]
- Ministry of Science/MICINN [IJCI-2017-33047]
- IRB
- Spanish Ministry of Economy
- European Regional Development Fund (ERDF) [SAF201348256-R]
- European Research Council [ERC-2014-AdG/669622]
- laCaixa Foundation
- Cancer Research U.K. (CRUK), Cambridge Centre Early Detection Programme
- CRUK Early Detection OHSU project [C62187/A26989]
- Medical Research Council (MRC) New Investigators Research Grant (NIRG) [MR/R000530/1]
- [CD19/00038]
- MRC [MR/R000530/1] Funding Source: UKRI
Advances in the detection of cellular senescence are crucial for monitoring age-related diseases, and the use of the HeckGal probe allows reliable detection of senescence both in vitro and in vivo. This technology provides a potential tool for detecting senescence in aged or damaged tissues.
Cellular senescence is a state of stable cell cycle arrest that can negatively affect the regenerative capacities of tissues and can contribute to inflammation and the progression of various aging-related diseases. Advances in the in vivo detection of cellular senescence are still crucial to monitor the action of senolytic drugs and to assess the early onset or accumulation of senescent cells. Here, we describe a naphthalimide-styrene-based probe (HeckGal) for the detection of cellular senescence both in vitro and in vivo. HeckGal is hydrolyzed by the increased lysosomal beta-galactosidase activity of senescent cells, resulting in fluorescence emission. The probe was validated in vitro using normal human fibroblasts and various cancer cell lines undergoing senescence induced by different stress stimuli. Remarkably, HeckGal was also validated in vivo in an orthotopic breast cancer mouse model treated with senescence-inducing chemotherapy and in a renal fibrosis mouse model. In all cases, HeckGal allowed the unambiguous detection of senescence in vitro as well as in tissues and tumors in vivo. This work is expected to provide a potential technology for senescence detection in aged or damaged tissues.
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