The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s

Detalhes bibliográficos
Autor(a) principal: Tamborlin, Leticia [UNESP]
Data de Publicação: 2023
Outros Autores: Pereira, Karina Danielle, Guimarães, Dimitrius Santiago Passos Simões Fróes, Silveira, Leonardo Reis, Luchessi, Augusto Ducati [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s00726-023-03283-4
http://hdl.handle.net/11449/247499
Resumo: Hypusine amino acid [N ε-(4-amino-2-hydroxybutyl)-lysine] was first isolated in 1971 from bovine brain extracts. Hypusine originates from a post-translational modification at the eukaryotic translation initiation factor 5A (eIF5A), a protein produced by archaebacteria and eukaryotes. The eIF5A protein is the only one described containing the hypusine residue, which is essential for its activity. Hypusine as a free amino acid is a consequence of proteolytic degradation of eIF5A. Herein, we showed, for the first time, evidence of biological activity for the free hypusine. C6 rat glioma cells were treated with hypusine, and different cellular parameters were evaluated. Hypusine treatment significantly reduced C6 cell proliferation and potently suppressed their clonogenic capacity without leading to apoptosis. Hypusine also decreased the Eif5A transcript content and the global protein synthesis profile that may occur due to negative feedback in response to high hypusine concentration, controlling the content of newly synthesized eIF5A, which can affect the translation process. Besides, hypusine treatment also altered cellular metabolism by changing the pathways for energy production, reducing cellular respiration coupled with oxidative phosphorylation, and increasing the anaerobic metabolism. These observed results and the relationship between eIF5A and tumor processes led us to test the combination of hypusine with the chemotherapeutic drug temozolomide. Combining temozolomide with hypusine reduced the MTT conversion to the same levels as those observed using double temozolomide dosage alone, demonstrating a synergetic action between the compounds. Thus, since 1971, this is the first study showing evidence of biological activity for hypusine not associated with being an essential component of the eiF5A protein. Finding out the molecular targets of hypusine are the following efforts to completely characterize its biological activity.
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spelling The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70sCell proliferationeIF5AHypusineOxidative metabolismPost-translational modificationProtein synthesisHypusine amino acid [N ε-(4-amino-2-hydroxybutyl)-lysine] was first isolated in 1971 from bovine brain extracts. Hypusine originates from a post-translational modification at the eukaryotic translation initiation factor 5A (eIF5A), a protein produced by archaebacteria and eukaryotes. The eIF5A protein is the only one described containing the hypusine residue, which is essential for its activity. Hypusine as a free amino acid is a consequence of proteolytic degradation of eIF5A. Herein, we showed, for the first time, evidence of biological activity for the free hypusine. C6 rat glioma cells were treated with hypusine, and different cellular parameters were evaluated. Hypusine treatment significantly reduced C6 cell proliferation and potently suppressed their clonogenic capacity without leading to apoptosis. Hypusine also decreased the Eif5A transcript content and the global protein synthesis profile that may occur due to negative feedback in response to high hypusine concentration, controlling the content of newly synthesized eIF5A, which can affect the translation process. Besides, hypusine treatment also altered cellular metabolism by changing the pathways for energy production, reducing cellular respiration coupled with oxidative phosphorylation, and increasing the anaerobic metabolism. These observed results and the relationship between eIF5A and tumor processes led us to test the combination of hypusine with the chemotherapeutic drug temozolomide. Combining temozolomide with hypusine reduced the MTT conversion to the same levels as those observed using double temozolomide dosage alone, demonstrating a synergetic action between the compounds. Thus, since 1971, this is the first study showing evidence of biological activity for hypusine not associated with being an essential component of the eiF5A protein. Finding out the molecular targets of hypusine are the following efforts to completely characterize its biological activity.Laboratory of Biotechnology School of Applied Sciences State University of Campinas (UNICAMP), Rua Pedro Zaccaria, 1300, Jardim Santa Luiza, São PauloInstitute of Biosciences São Paulo State University (UNESP), São PauloObesity and Comorbidities Research Center Department of Structural and Functional Biology State University of Campinas (UNICAMP), São PauloInstitute of Biosciences São Paulo State University (UNESP), São PauloUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (UNESP)Tamborlin, Leticia [UNESP]Pereira, Karina DanielleGuimarães, Dimitrius Santiago Passos Simões FróesSilveira, Leonardo ReisLuchessi, Augusto Ducati [UNESP]2023-07-29T13:17:48Z2023-07-29T13:17:48Z2023-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1007/s00726-023-03283-4Amino Acids.1438-21990939-4451http://hdl.handle.net/11449/24749910.1007/s00726-023-03283-42-s2.0-85160793270Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAmino Acidsinfo:eu-repo/semantics/openAccess2023-07-29T13:17:48Zoai:repositorio.unesp.br:11449/247499Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:03:02.838541Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
title The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
spellingShingle The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
Tamborlin, Leticia [UNESP]
Cell proliferation
eIF5A
Hypusine
Oxidative metabolism
Post-translational modification
Protein synthesis
title_short The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
title_full The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
title_fullStr The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
title_full_unstemmed The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
title_sort The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
author Tamborlin, Leticia [UNESP]
author_facet Tamborlin, Leticia [UNESP]
Pereira, Karina Danielle
Guimarães, Dimitrius Santiago Passos Simões Fróes
Silveira, Leonardo Reis
Luchessi, Augusto Ducati [UNESP]
author_role author
author2 Pereira, Karina Danielle
Guimarães, Dimitrius Santiago Passos Simões Fróes
Silveira, Leonardo Reis
Luchessi, Augusto Ducati [UNESP]
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Campinas (UNICAMP)
Universidade Estadual Paulista (UNESP)
dc.contributor.author.fl_str_mv Tamborlin, Leticia [UNESP]
Pereira, Karina Danielle
Guimarães, Dimitrius Santiago Passos Simões Fróes
Silveira, Leonardo Reis
Luchessi, Augusto Ducati [UNESP]
dc.subject.por.fl_str_mv Cell proliferation
eIF5A
Hypusine
Oxidative metabolism
Post-translational modification
Protein synthesis
topic Cell proliferation
eIF5A
Hypusine
Oxidative metabolism
Post-translational modification
Protein synthesis
description Hypusine amino acid [N ε-(4-amino-2-hydroxybutyl)-lysine] was first isolated in 1971 from bovine brain extracts. Hypusine originates from a post-translational modification at the eukaryotic translation initiation factor 5A (eIF5A), a protein produced by archaebacteria and eukaryotes. The eIF5A protein is the only one described containing the hypusine residue, which is essential for its activity. Hypusine as a free amino acid is a consequence of proteolytic degradation of eIF5A. Herein, we showed, for the first time, evidence of biological activity for the free hypusine. C6 rat glioma cells were treated with hypusine, and different cellular parameters were evaluated. Hypusine treatment significantly reduced C6 cell proliferation and potently suppressed their clonogenic capacity without leading to apoptosis. Hypusine also decreased the Eif5A transcript content and the global protein synthesis profile that may occur due to negative feedback in response to high hypusine concentration, controlling the content of newly synthesized eIF5A, which can affect the translation process. Besides, hypusine treatment also altered cellular metabolism by changing the pathways for energy production, reducing cellular respiration coupled with oxidative phosphorylation, and increasing the anaerobic metabolism. These observed results and the relationship between eIF5A and tumor processes led us to test the combination of hypusine with the chemotherapeutic drug temozolomide. Combining temozolomide with hypusine reduced the MTT conversion to the same levels as those observed using double temozolomide dosage alone, demonstrating a synergetic action between the compounds. Thus, since 1971, this is the first study showing evidence of biological activity for hypusine not associated with being an essential component of the eiF5A protein. Finding out the molecular targets of hypusine are the following efforts to completely characterize its biological activity.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T13:17:48Z
2023-07-29T13:17:48Z
2023-01-01
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://dx.doi.org/10.1007/s00726-023-03283-4
Amino Acids.
1438-2199
0939-4451
http://hdl.handle.net/11449/247499
10.1007/s00726-023-03283-4
2-s2.0-85160793270
url http://dx.doi.org/10.1007/s00726-023-03283-4
http://hdl.handle.net/11449/247499
identifier_str_mv Amino Acids.
1438-2199
0939-4451
10.1007/s00726-023-03283-4
2-s2.0-85160793270
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Amino Acids
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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