The role of NAD metabolism in neuronal differentiation

Detalhes bibliográficos
Autor(a) principal: Neves, Diogo
Data de Publicação: 2022
Outros Autores: Goodfellow, Brian J., Vieira, Sandra I., Silva, Raquel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.14/38358
Resumo: Background: Nicotinamide adenine dinucleotide (NAD) metabolism is involved in redox and non-redox reactions that regulate several processes including differentiation of cells of different origins. Here, the role of NAD metabolism in neuronal differentiation, which remains elusive so far, was investigated. Material and methods: A protein-protein interaction network between neurotrophin signaling and NAD metabolic pathways was built. Expression of NAD biosynthetic enzymes in SH-SY5Y cells during retinoic acid (RA)/brain derived neurotrophic factor (BDNF) differentiation, was evaluated. The effects of NAD biosynthetic enzymes QPRT and NAPRT inhibition in neurite outgrowth, cell viability, NAD availability and histone deacetylase (HDAC) activity, were analysed in RA- and BDNF-differentiated cells. Results: Bioinformatics analysis revealed the interaction between NAD biosynthetic enzyme NMNAT1 and NTRK2, a receptor activated by RA/BDNF sequential treatment. Differences were found in the expression of NAD biosynthetic enzymes during neuronal differentiation, namely, increased QPRT gene expression along the course of RA/BDNF treatment and NAPRT protein expression after a 5-day treatment with RA. QPRT inhibition in BDNF-differentiated SH-SY5Y cells resulted in less neuritic length per cell, decreased expression of the neuronal marker β-III Tubulin and also decreased NAD+ levels and HDAC activity. NAPRT inhibition had no effect in neuritic length per cell, NAD+ levels and HDAC activity. Of note, NAD supplementation along with RA, but not with BDNF, resulted in considerable cell death. Conclusions: Taken together, our results show the involvement of NAD metabolism in neuronal differentiation, specifically, the importance of QPRT-mediated NAD biosynthesis in BDNF-associated SH-SY5Y differentiation and suggest additional roles for NAPRT beyond NAD production in RA-differentiated cells.
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spelling The role of NAD metabolism in neuronal differentiationNeuronal differentiationNeuritogenesisNADNAPRTQPRTNeural regenerationBackground: Nicotinamide adenine dinucleotide (NAD) metabolism is involved in redox and non-redox reactions that regulate several processes including differentiation of cells of different origins. Here, the role of NAD metabolism in neuronal differentiation, which remains elusive so far, was investigated. Material and methods: A protein-protein interaction network between neurotrophin signaling and NAD metabolic pathways was built. Expression of NAD biosynthetic enzymes in SH-SY5Y cells during retinoic acid (RA)/brain derived neurotrophic factor (BDNF) differentiation, was evaluated. The effects of NAD biosynthetic enzymes QPRT and NAPRT inhibition in neurite outgrowth, cell viability, NAD availability and histone deacetylase (HDAC) activity, were analysed in RA- and BDNF-differentiated cells. Results: Bioinformatics analysis revealed the interaction between NAD biosynthetic enzyme NMNAT1 and NTRK2, a receptor activated by RA/BDNF sequential treatment. Differences were found in the expression of NAD biosynthetic enzymes during neuronal differentiation, namely, increased QPRT gene expression along the course of RA/BDNF treatment and NAPRT protein expression after a 5-day treatment with RA. QPRT inhibition in BDNF-differentiated SH-SY5Y cells resulted in less neuritic length per cell, decreased expression of the neuronal marker β-III Tubulin and also decreased NAD+ levels and HDAC activity. NAPRT inhibition had no effect in neuritic length per cell, NAD+ levels and HDAC activity. Of note, NAD supplementation along with RA, but not with BDNF, resulted in considerable cell death. Conclusions: Taken together, our results show the involvement of NAD metabolism in neuronal differentiation, specifically, the importance of QPRT-mediated NAD biosynthesis in BDNF-associated SH-SY5Y differentiation and suggest additional roles for NAPRT beyond NAD production in RA-differentiated cells.Veritati - Repositório Institucional da Universidade Católica PortuguesaNeves, DiogoGoodfellow, Brian J.Vieira, Sandra I.Silva, Raquel2022-10-012022-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/38358eng0197-018610.1016/j.neuint.2022.1054028513552810935843422000862413100004info: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:RCAAP2024-01-16T01:44:22Zoai:repositorio.ucp.pt:10400.14/38358Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:31:18.908948Repositório 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 The role of NAD metabolism in neuronal differentiation
title The role of NAD metabolism in neuronal differentiation
spellingShingle The role of NAD metabolism in neuronal differentiation
Neves, Diogo
Neuronal differentiation
Neuritogenesis
NAD
NAPRT
QPRT
Neural regeneration
title_short The role of NAD metabolism in neuronal differentiation
title_full The role of NAD metabolism in neuronal differentiation
title_fullStr The role of NAD metabolism in neuronal differentiation
title_full_unstemmed The role of NAD metabolism in neuronal differentiation
title_sort The role of NAD metabolism in neuronal differentiation
author Neves, Diogo
author_facet Neves, Diogo
Goodfellow, Brian J.
Vieira, Sandra I.
Silva, Raquel
author_role author
author2 Goodfellow, Brian J.
Vieira, Sandra I.
Silva, Raquel
author2_role author
author
author
dc.contributor.none.fl_str_mv Veritati - Repositório Institucional da Universidade Católica Portuguesa
dc.contributor.author.fl_str_mv Neves, Diogo
Goodfellow, Brian J.
Vieira, Sandra I.
Silva, Raquel
dc.subject.por.fl_str_mv Neuronal differentiation
Neuritogenesis
NAD
NAPRT
QPRT
Neural regeneration
topic Neuronal differentiation
Neuritogenesis
NAD
NAPRT
QPRT
Neural regeneration
description Background: Nicotinamide adenine dinucleotide (NAD) metabolism is involved in redox and non-redox reactions that regulate several processes including differentiation of cells of different origins. Here, the role of NAD metabolism in neuronal differentiation, which remains elusive so far, was investigated. Material and methods: A protein-protein interaction network between neurotrophin signaling and NAD metabolic pathways was built. Expression of NAD biosynthetic enzymes in SH-SY5Y cells during retinoic acid (RA)/brain derived neurotrophic factor (BDNF) differentiation, was evaluated. The effects of NAD biosynthetic enzymes QPRT and NAPRT inhibition in neurite outgrowth, cell viability, NAD availability and histone deacetylase (HDAC) activity, were analysed in RA- and BDNF-differentiated cells. Results: Bioinformatics analysis revealed the interaction between NAD biosynthetic enzyme NMNAT1 and NTRK2, a receptor activated by RA/BDNF sequential treatment. Differences were found in the expression of NAD biosynthetic enzymes during neuronal differentiation, namely, increased QPRT gene expression along the course of RA/BDNF treatment and NAPRT protein expression after a 5-day treatment with RA. QPRT inhibition in BDNF-differentiated SH-SY5Y cells resulted in less neuritic length per cell, decreased expression of the neuronal marker β-III Tubulin and also decreased NAD+ levels and HDAC activity. NAPRT inhibition had no effect in neuritic length per cell, NAD+ levels and HDAC activity. Of note, NAD supplementation along with RA, but not with BDNF, resulted in considerable cell death. Conclusions: Taken together, our results show the involvement of NAD metabolism in neuronal differentiation, specifically, the importance of QPRT-mediated NAD biosynthesis in BDNF-associated SH-SY5Y differentiation and suggest additional roles for NAPRT beyond NAD production in RA-differentiated cells.
publishDate 2022
dc.date.none.fl_str_mv 2022-10-01
2022-10-01T00:00:00Z
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.14/38358
url http://hdl.handle.net/10400.14/38358
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0197-0186
10.1016/j.neuint.2022.105402
85135528109
35843422
000862413100004
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