The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Research, Society and Development |
DOI: | 10.33448/rsd-v11i3.26787 |
Texto Completo: | https://rsdjournal.org/index.php/rsd/article/view/26787 |
Resumo: | Introduction: The knowledge about the biology of obesity and apoptosis induction of adipose-derived stem cells (ADSCs) may support in the development of new therapies. Objective: The present research aimed to investigate the toxicogenic effect of all-trans retinoic acid (ATRA) as well as its influence in the adipogenic differentiation and expression of genes related to DNA damage, cell cycle and thermogenesis. Methodology: Cell cultures of human adipose-derived stem cells were treated for 12 hours with ATRA (20.75 μM) and were performed the adipogenic differentiation, comet assay, micronucleous, cell death, cell cycle and qPCR. Results: The ATRA treatment decreased the capacity of adipogenic differentiation of ADSCs. The comet assay demonstrated increase in nucleoid frequency with genomic damage and scoring. However, these damages were not fixed at the chromosome level, since the tail moment was not significant. The treatment with ATRA increased cytotoxicity and increased cell death by apoptosis. The relative expression of CHEK-1, CHEK-2, CDC25A, CDC25C, ATM and ATR decreased and only UCP1 increased significantly. Conclusion: The results of the present study demonstrate that the use of ATRA induces genomic damage in ADSCs, although it was eliminated in the apoptosis process. Therefore, administration of ATRA in ADSCs did not cause chromosomal instability, which suggests toxicogenic safety. Also it was considered that ATRA might active the browning effect. Thus, this compound is considered a promising candidate for the development of novel therapies for the treatment of obesity and / or localized fat by the use of mesotherapy. |
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Research, Society and Development |
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The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process El tratamiento con ácido retinoico todo trans provoca apoptosis sin inestabilidad cromosómica en células madre derivadas de tejido adiposo y puede actuar iniciando el proceso de oscurecimientoO tratamento com ácido all-trans retinóico causa apoptose sem instabilidade cromossômica em células-tronco derivadas do tecido adiposo e pode atuar iniciando o processo de escurecimentoMesoterapiaCitotoxicidadCélulas madreATRAOscureciendo.MesotherapyCytotoxicityAdipose-derived stem cellsATRABrowning.MesoterapiaCitotoxicidadeCélulas-troncoATRAEscurecimento.Introduction: The knowledge about the biology of obesity and apoptosis induction of adipose-derived stem cells (ADSCs) may support in the development of new therapies. Objective: The present research aimed to investigate the toxicogenic effect of all-trans retinoic acid (ATRA) as well as its influence in the adipogenic differentiation and expression of genes related to DNA damage, cell cycle and thermogenesis. Methodology: Cell cultures of human adipose-derived stem cells were treated for 12 hours with ATRA (20.75 μM) and were performed the adipogenic differentiation, comet assay, micronucleous, cell death, cell cycle and qPCR. Results: The ATRA treatment decreased the capacity of adipogenic differentiation of ADSCs. The comet assay demonstrated increase in nucleoid frequency with genomic damage and scoring. However, these damages were not fixed at the chromosome level, since the tail moment was not significant. The treatment with ATRA increased cytotoxicity and increased cell death by apoptosis. The relative expression of CHEK-1, CHEK-2, CDC25A, CDC25C, ATM and ATR decreased and only UCP1 increased significantly. Conclusion: The results of the present study demonstrate that the use of ATRA induces genomic damage in ADSCs, although it was eliminated in the apoptosis process. Therefore, administration of ATRA in ADSCs did not cause chromosomal instability, which suggests toxicogenic safety. Also it was considered that ATRA might active the browning effect. Thus, this compound is considered a promising candidate for the development of novel therapies for the treatment of obesity and / or localized fat by the use of mesotherapy.Introducción: El conocimiento sobre la biología de la obesidad y la inducción de apoptosis de células madre derivadas del tejido adiposo humano puede ayudar en el desarrollo de nuevas terapias. Objetivo: La presente investigación tuvo como objetivo investigar el efecto toxicogenético del ácido transretinoico (ATRA), así como su influencia en la diferenciación adipogénica y la expresión de genes relacionados con el daño del ADN, el ciclo celular y la termogénesis. Metodología: Los cultivos celulares de células madre se trataron durante 12 horas con ATRA (20.75 μM) y se realizó diferenciación adipogénica, ensayo cometa, micronúcleo, muerte celular, ciclo celular y qPCR. Resultados: El tratamiento con ATRA disminuyó la capacidad de diferenciación adipogénica de las células madre. El ensayo del cometa demostró un aumento en la frecuencia de nucleoides con daño genómico. Sin embargo, estos daños no se fijaron a nivel cromosómico, ya que el momento de la cola no fue significativo. El tratamiento con ATRA aumentó la citotoxicidad y aumentó la muerte celular por apoptosis. La expresión relativa de CHEK-1, CHEK-2, CDC25A, CDC25C, ATM y ATR disminuyó y solo UCP1 aumentó significativamente. Conclusión: Los resultados del presente estudio demuestran que el uso de ATRA induce daño genómico en células madre, pero se elimina con el proceso de apoptosis. La administración de ATRA no causó inestabilidad cromosómica, lo que sugiere seguridad toxicogenética. También se consideró que ATRA puede activar el efecto de oscurecimiento de estas células. Así, este compuesto se considera un candidato prometedor para el desarrollo de nuevas terapias para el tratamiento de la obesidad y/o grasa localizada mediante el uso de mesoterapia.Introdução: O conhecimento sobre a biologia da obesidade e indução de apoptose de células-tronco derivadas do tecido adiposo humano pode auxiliar no desenvolvimento de novas terapias. Objetivo: A presente pesquisa teve como objetivo investigar o efeito toxicogenético do ácido all-trans retinóico (ATRA), bem como sua influência na diferenciação adipogênica e expressão de genes relacionados a danos no DNA, ciclo celular e termogênese. Metodologia: Culturas celulares de células-tronco foram tratadas por 12 horas com ATRA (20,75 μM) e foram realizadas a diferenciação adipogênica, ensaio cometa, micronúcleo, morte celular, ciclo celular e qPCR. Resultados: O tratamento com ATRA diminuiu a capacidade de diferenciação adipogênica das células-tronco. O ensaio do cometa demonstrou aumento na frequência de nucleóides com dano genômico. No entanto, esses danos não foram fixados no nível cromossômico, uma vez que o momento de cauda não foi significativo. O tratamento com ATRA aumentou a citotoxicidade e aumentou a morte celular por apoptose. A expressão relativa de CHEK-1, CHEK-2, CDC25A, CDC25C, ATM e ATR diminuiu e apenas UCP1 aumentou significativamente. Conclusão: Os resultados do presente estudo demonstram que o uso de ATRA induz danos genômicos em células-tronco, porém são eliminados com o processo de apoptose. A administração de ATRA não causou instabilidade cromossômica, o que sugere segurança toxicogenética. Também foi considerado que o ATRA pode ativar o efeito de escurecimento dessas células. Assim, este composto é considerado um candidato promissor para o desenvolvimento de novas terapias para o tratamento da obesidade e/ou gordura localizada pelo uso da mesoterapia.Research, Society and Development2022-03-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://rsdjournal.org/index.php/rsd/article/view/2678710.33448/rsd-v11i3.26787Research, Society and Development; Vol. 11 No. 3; e53511326787Research, Society and Development; Vol. 11 Núm. 3; e53511326787Research, Society and Development; v. 11 n. 3; e535113267872525-3409reponame:Research, Society and Developmentinstname:Universidade Federal de Itajubá (UNIFEI)instacron:UNIFEIenghttps://rsdjournal.org/index.php/rsd/article/view/26787/23516Copyright (c) 2022 Laynna de Carvalho Schweich-Adami; Andréia Conceição Milan Brochado Antoniolli-Silva; Rodrigo Juliano Oliveirahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessSchweich-Adami, Laynna de Carvalho Antoniolli-Silva, Andréia Conceição Milan Brochado Oliveira, Rodrigo Juliano2022-03-09T13:44:38Zoai:ojs.pkp.sfu.ca:article/26787Revistahttps://rsdjournal.org/index.php/rsd/indexPUBhttps://rsdjournal.org/index.php/rsd/oairsd.articles@gmail.com2525-34092525-3409opendoar:2024-01-17T09:44:44.540117Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)false |
dc.title.none.fl_str_mv |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process El tratamiento con ácido retinoico todo trans provoca apoptosis sin inestabilidad cromosómica en células madre derivadas de tejido adiposo y puede actuar iniciando el proceso de oscurecimiento O tratamento com ácido all-trans retinóico causa apoptose sem instabilidade cromossômica em células-tronco derivadas do tecido adiposo e pode atuar iniciando o processo de escurecimento |
title |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process |
spellingShingle |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process Schweich-Adami, Laynna de Carvalho Mesoterapia Citotoxicidad Células madre ATRA Oscureciendo. Mesotherapy Cytotoxicity Adipose-derived stem cells ATRA Browning. Mesoterapia Citotoxicidade Células-tronco ATRA Escurecimento. Schweich-Adami, Laynna de Carvalho Mesoterapia Citotoxicidad Células madre ATRA Oscureciendo. Mesotherapy Cytotoxicity Adipose-derived stem cells ATRA Browning. Mesoterapia Citotoxicidade Células-tronco ATRA Escurecimento. |
title_short |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process |
title_full |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process |
title_fullStr |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process |
title_full_unstemmed |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process |
title_sort |
The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process |
author |
Schweich-Adami, Laynna de Carvalho |
author_facet |
Schweich-Adami, Laynna de Carvalho Schweich-Adami, Laynna de Carvalho Antoniolli-Silva, Andréia Conceição Milan Brochado Oliveira, Rodrigo Juliano Antoniolli-Silva, Andréia Conceição Milan Brochado Oliveira, Rodrigo Juliano |
author_role |
author |
author2 |
Antoniolli-Silva, Andréia Conceição Milan Brochado Oliveira, Rodrigo Juliano |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Schweich-Adami, Laynna de Carvalho Antoniolli-Silva, Andréia Conceição Milan Brochado Oliveira, Rodrigo Juliano |
dc.subject.por.fl_str_mv |
Mesoterapia Citotoxicidad Células madre ATRA Oscureciendo. Mesotherapy Cytotoxicity Adipose-derived stem cells ATRA Browning. Mesoterapia Citotoxicidade Células-tronco ATRA Escurecimento. |
topic |
Mesoterapia Citotoxicidad Células madre ATRA Oscureciendo. Mesotherapy Cytotoxicity Adipose-derived stem cells ATRA Browning. Mesoterapia Citotoxicidade Células-tronco ATRA Escurecimento. |
description |
Introduction: The knowledge about the biology of obesity and apoptosis induction of adipose-derived stem cells (ADSCs) may support in the development of new therapies. Objective: The present research aimed to investigate the toxicogenic effect of all-trans retinoic acid (ATRA) as well as its influence in the adipogenic differentiation and expression of genes related to DNA damage, cell cycle and thermogenesis. Methodology: Cell cultures of human adipose-derived stem cells were treated for 12 hours with ATRA (20.75 μM) and were performed the adipogenic differentiation, comet assay, micronucleous, cell death, cell cycle and qPCR. Results: The ATRA treatment decreased the capacity of adipogenic differentiation of ADSCs. The comet assay demonstrated increase in nucleoid frequency with genomic damage and scoring. However, these damages were not fixed at the chromosome level, since the tail moment was not significant. The treatment with ATRA increased cytotoxicity and increased cell death by apoptosis. The relative expression of CHEK-1, CHEK-2, CDC25A, CDC25C, ATM and ATR decreased and only UCP1 increased significantly. Conclusion: The results of the present study demonstrate that the use of ATRA induces genomic damage in ADSCs, although it was eliminated in the apoptosis process. Therefore, administration of ATRA in ADSCs did not cause chromosomal instability, which suggests toxicogenic safety. Also it was considered that ATRA might active the browning effect. Thus, this compound is considered a promising candidate for the development of novel therapies for the treatment of obesity and / or localized fat by the use of mesotherapy. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-03-07 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/26787 10.33448/rsd-v11i3.26787 |
url |
https://rsdjournal.org/index.php/rsd/article/view/26787 |
identifier_str_mv |
10.33448/rsd-v11i3.26787 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/26787/23516 |
dc.rights.driver.fl_str_mv |
https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Research, Society and Development |
publisher.none.fl_str_mv |
Research, Society and Development |
dc.source.none.fl_str_mv |
Research, Society and Development; Vol. 11 No. 3; e53511326787 Research, Society and Development; Vol. 11 Núm. 3; e53511326787 Research, Society and Development; v. 11 n. 3; e53511326787 2525-3409 reponame:Research, Society and Development instname:Universidade Federal de Itajubá (UNIFEI) instacron:UNIFEI |
instname_str |
Universidade Federal de Itajubá (UNIFEI) |
instacron_str |
UNIFEI |
institution |
UNIFEI |
reponame_str |
Research, Society and Development |
collection |
Research, Society and Development |
repository.name.fl_str_mv |
Research, Society and Development - Universidade Federal de Itajubá (UNIFEI) |
repository.mail.fl_str_mv |
rsd.articles@gmail.com |
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1822178728247033856 |
dc.identifier.doi.none.fl_str_mv |
10.33448/rsd-v11i3.26787 |