A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis
Abstract Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-44903-1 |
| _version_ | 1797276450841165824 |
|---|---|
| author | Sara Rojas-Vázquez Beatriz Lozano-Torres Alba García-Fernández Irene Galiana Ana Perez-Villalba Pablo Martí-Rodrigo M. José Palop Marcia Domínguez Mar Orzáez Félix Sancenón Juan F. Blandez Isabel Fariñas Ramón Martínez-Máñez |
| author_facet | Sara Rojas-Vázquez Beatriz Lozano-Torres Alba García-Fernández Irene Galiana Ana Perez-Villalba Pablo Martí-Rodrigo M. José Palop Marcia Domínguez Mar Orzáez Félix Sancenón Juan F. Blandez Isabel Fariñas Ramón Martínez-Máñez |
| author_sort | Sara Rojas-Vázquez |
| collection | DOAJ |
| description | Abstract Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for β-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, β-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids. |
| first_indexed | 2024-03-07T15:28:24Z |
| format | Article |
| id | doaj.art-1498936e271e4859a089a88d0502ed20 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T15:28:24Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-1498936e271e4859a089a88d0502ed202024-03-05T16:34:31ZengNature PortfolioNature Communications2041-17232024-01-0115111610.1038/s41467-024-44903-1A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysisSara Rojas-Vázquez0Beatriz Lozano-Torres1Alba García-Fernández2Irene Galiana3Ana Perez-Villalba4Pablo Martí-Rodrigo5M. José Palop6Marcia Domínguez7Mar Orzáez8Félix Sancenón9Juan F. Blandez10Isabel Fariñas11Ramón Martínez-Máñez12Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaLaboratory of Animal Behavior Phenotype (L.A.B.P.). Facultad de Psicología, Universidad Católica de ValenciaInstituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de ValènciaInstituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de ValènciaInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaUnidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe FelipeInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaInstituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de ValènciaInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València-Universitat de ValènciaAbstract Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for β-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, β-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids.https://doi.org/10.1038/s41467-024-44903-1 |
| spellingShingle | Sara Rojas-Vázquez Beatriz Lozano-Torres Alba García-Fernández Irene Galiana Ana Perez-Villalba Pablo Martí-Rodrigo M. José Palop Marcia Domínguez Mar Orzáez Félix Sancenón Juan F. Blandez Isabel Fariñas Ramón Martínez-Máñez A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis Nature Communications |
| title | A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis |
| title_full | A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis |
| title_fullStr | A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis |
| title_full_unstemmed | A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis |
| title_short | A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis |
| title_sort | renal clearable fluorogenic probe for in vivo β galactosidase activity detection during aging and senolysis |
| url | https://doi.org/10.1038/s41467-024-44903-1 |
| work_keys_str_mv | AT sararojasvazquez arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT beatrizlozanotorres arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT albagarciafernandez arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT irenegaliana arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT anaperezvillalba arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT pablomartirodrigo arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT mjosepalop arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT marciadominguez arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT marorzaez arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT felixsancenon arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT juanfblandez arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT isabelfarinas arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT ramonmartinezmanez arenalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT sararojasvazquez renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT beatrizlozanotorres renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT albagarciafernandez renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT irenegaliana renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT anaperezvillalba renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT pablomartirodrigo renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT mjosepalop renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT marciadominguez renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT marorzaez renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT felixsancenon renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT juanfblandez renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT isabelfarinas renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis AT ramonmartinezmanez renalclearablefluorogenicprobeforinvivobgalactosidaseactivitydetectionduringagingandsenolysis |