The first evidence of biological activity for free Hypusine, an enigmatic amino acid discovered in the '70s
Autor(a) principal: | |
---|---|
Data de Publicação: | 2023 |
Outros Autores: | , , , |
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. |
id |
UNSP_810a8363aa252d0e488701bb93bbeb3d |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/247499 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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) |
repository.mail.fl_str_mv |
|
_version_ |
1808128232456716288 |