Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/103323 https://doi.org/10.3390/ijms23063009 |
Resumo: | With the increase in life expectancy and consequent aging of the world's population, the prevalence of many neurodegenerative diseases is increasing, without concomitant improvement in diagnostics and therapeutics. These diseases share neuropathological hallmarks, including mitochondrial dysfunction. In fact, as mitochondrial alterations appear prior to neuronal cell death at an early phase of a disease's onset, the study and modulation of mitochondrial alterations have emerged as promising strategies to predict and prevent neurotoxicity and neuronal cell death before the onset of cell viability alterations. In this work, differentiated SH-SY5Y cells were treated with the mitochondrial-targeted neurotoxicants 6-hydroxydopamine and rotenone. These compounds were used at different concentrations and for different time points to understand the similarities and differences in their mechanisms of action. To accomplish this, data on mitochondrial parameters were acquired and analyzed using unsupervised (hierarchical clustering) and supervised (decision tree) machine learning methods. Both biochemical and computational analyses resulted in an evident distinction between the neurotoxic effects of 6-hydroxydopamine and rotenone, specifically for the highest concentrations of both compounds. |
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Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics6-hydroxydopaminerotenonein vitro neurotoxicitymitochondrial dysfunctionexploratory data analysisapplied computational statisticsunsupervised and supervised machine learningApoptosisCell DeathCell Line, TumorCell SurvivalHumansOxidopamineRotenoneNeuroprotective AgentsNeurotoxicity SyndromesWith the increase in life expectancy and consequent aging of the world's population, the prevalence of many neurodegenerative diseases is increasing, without concomitant improvement in diagnostics and therapeutics. These diseases share neuropathological hallmarks, including mitochondrial dysfunction. In fact, as mitochondrial alterations appear prior to neuronal cell death at an early phase of a disease's onset, the study and modulation of mitochondrial alterations have emerged as promising strategies to predict and prevent neurotoxicity and neuronal cell death before the onset of cell viability alterations. In this work, differentiated SH-SY5Y cells were treated with the mitochondrial-targeted neurotoxicants 6-hydroxydopamine and rotenone. These compounds were used at different concentrations and for different time points to understand the similarities and differences in their mechanisms of action. To accomplish this, data on mitochondrial parameters were acquired and analyzed using unsupervised (hierarchical clustering) and supervised (decision tree) machine learning methods. Both biochemical and computational analyses resulted in an evident distinction between the neurotoxic effects of 6-hydroxydopamine and rotenone, specifically for the highest concentrations of both compounds.This research was funded by the European Regional Development Fund (ERDF), through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, under projects, PTDC/MEDFAR/ 29391/2017, POCI-01-0145-FEDER-029391, PTDC/BTM-SAL/29297/2017, POCI-01-0145-FEDER- 029297, PTDC/BTM-ORG/0055/2021, DL57/2016/CP1448/CT0016 [TCO], UIDP/04539/2020 (CNC), UIDB/04539/2020 (CNC), and UID/CEC/00326/2020 (CISUC).2022-03-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103323http://hdl.handle.net/10316/103323https://doi.org/10.3390/ijms23063009eng1422-0067Simões, Rui F.Oliveira, Paulo J.Oliveira, Teresa CunhaPereira, Francisco B.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-06T10:20:17Zoai:estudogeral.uc.pt:10316/103323Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:10.785797Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
title |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
spellingShingle |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics Simões, Rui F. 6-hydroxydopamine rotenone in vitro neurotoxicity mitochondrial dysfunction exploratory data analysis applied computational statistics unsupervised and supervised machine learning Apoptosis Cell Death Cell Line, Tumor Cell Survival Humans Oxidopamine Rotenone Neuroprotective Agents Neurotoxicity Syndromes |
title_short |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
title_full |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
title_fullStr |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
title_full_unstemmed |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
title_sort |
Evaluation of 6-Hydroxydopamine and Rotenone In Vitro Neurotoxicity on Differentiated SH-SY5Y Cells Using Applied Computational Statistics |
author |
Simões, Rui F. |
author_facet |
Simões, Rui F. Oliveira, Paulo J. Oliveira, Teresa Cunha Pereira, Francisco B. |
author_role |
author |
author2 |
Oliveira, Paulo J. Oliveira, Teresa Cunha Pereira, Francisco B. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Simões, Rui F. Oliveira, Paulo J. Oliveira, Teresa Cunha Pereira, Francisco B. |
dc.subject.por.fl_str_mv |
6-hydroxydopamine rotenone in vitro neurotoxicity mitochondrial dysfunction exploratory data analysis applied computational statistics unsupervised and supervised machine learning Apoptosis Cell Death Cell Line, Tumor Cell Survival Humans Oxidopamine Rotenone Neuroprotective Agents Neurotoxicity Syndromes |
topic |
6-hydroxydopamine rotenone in vitro neurotoxicity mitochondrial dysfunction exploratory data analysis applied computational statistics unsupervised and supervised machine learning Apoptosis Cell Death Cell Line, Tumor Cell Survival Humans Oxidopamine Rotenone Neuroprotective Agents Neurotoxicity Syndromes |
description |
With the increase in life expectancy and consequent aging of the world's population, the prevalence of many neurodegenerative diseases is increasing, without concomitant improvement in diagnostics and therapeutics. These diseases share neuropathological hallmarks, including mitochondrial dysfunction. In fact, as mitochondrial alterations appear prior to neuronal cell death at an early phase of a disease's onset, the study and modulation of mitochondrial alterations have emerged as promising strategies to predict and prevent neurotoxicity and neuronal cell death before the onset of cell viability alterations. In this work, differentiated SH-SY5Y cells were treated with the mitochondrial-targeted neurotoxicants 6-hydroxydopamine and rotenone. These compounds were used at different concentrations and for different time points to understand the similarities and differences in their mechanisms of action. To accomplish this, data on mitochondrial parameters were acquired and analyzed using unsupervised (hierarchical clustering) and supervised (decision tree) machine learning methods. Both biochemical and computational analyses resulted in an evident distinction between the neurotoxic effects of 6-hydroxydopamine and rotenone, specifically for the highest concentrations of both compounds. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-03-10 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/103323 http://hdl.handle.net/10316/103323 https://doi.org/10.3390/ijms23063009 |
url |
http://hdl.handle.net/10316/103323 https://doi.org/10.3390/ijms23063009 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1422-0067 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134095117123584 |