Nuclear inclusions of pathogenic ataxin-1 induce oxidative
stress and perturb the protein synthesis machinery

J 2020

Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

LAIDOU, Stamatia, Gregorio ALANIS-LOBATO, Jan PŘIBYL, Tamás RASKÓ, Boris TICHÝ et. al.

Základní údaje

Originální název

Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

Autoři

LAIDOU, Stamatia, Gregorio ALANIS-LOBATO, Jan PŘIBYL (203 Česká republika, domácí), Tamás RASKÓ, Boris TICHÝ (203 Česká republika, domácí), Kamil MIKULÁŠEK (203 Česká republika, domácí), Maria TSAGIOPOULOU, Jan OPPELT (203 Česká republika, domácí), Georgia KASTRINAKI, Maria LEFAKI, Manvendra SINGH, Annika ZINK, Niki CHONDROGIANNI, Fotis PSOMOPOULOS, Alessandro PRIGIONE, Zoltan IVICS, Šárka POSPÍŠILOVÁ (203 Česká republika, domácí), Petr SKLÁDAL (203 Česká republika, domácí), Zsuzsanna IZSVAK, Miguel A. ANDRADE-NAVARRO a Spyros PETRAKIS

Vydání

Redox Biology, Amsterdam, Elsevier, 2020, 2213-2317

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.799

Kód RIV

RIV/00216224:14740/20:00116844

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1016/j.redox.2020.101458

UT WoS

000537459900001

Klíčová slova anglicky

Ataxin-1; Polyglutamine; Sleeping beauty transposon; Oxidative stress; Protein network; Ribosome

Štítky

CF BIOIT, CF GEN, CF NANO, CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 10. 2024 09:20, Ing. Martina Blahová

Anotace

V originále

Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expression of the mutant protein. We characterized the structure and the protein composition of insoluble polyQ IIBs which gradually occupy the nuclei and are responsible for the generation of reactive oxygen species. In response to their formation, our transcriptome analysis reveals a cerebellum-specific perturbed protein interaction network, primarily affecting protein synthesis. We propose that insoluble polyQ IIBs cause oxidative and nucleolar stress and affect the assembly of the ribosome by capturing or down-regulating essential components. The inducible cell system can be utilized to decipher the cellular consequences of polyQ protein aggregation. Our strategy provides a broadly applicable methodology for studying polyQ diseases.

Návaznosti

EF16_013/0001776, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii pro lidské zdraví

LM2018127, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

692298, interní kód MU

Název: MEDGENET - Medical genomics and epigenomics network (Akronym: MEDGENET)

Investor: Evropská unie, MEDGENET - Medical genomics and epigenomics network, Spreading excellence and widening participation

90127, velká výzkumná infrastruktura

Název: CIISB II

90132, velká výzkumná infrastruktura

Název: NCMG II

Citovat

LAIDOU, Stamatia, Gregorio ALANIS-LOBATO, Jan PŘIBYL, Tamás RASKÓ, Boris TICHÝ, Kamil MIKULÁŠEK, Maria TSAGIOPOULOU, Jan OPPELT, Georgia KASTRINAKI, Maria LEFAKI, Manvendra SINGH, Annika ZINK, Niki CHONDROGIANNI, Fotis PSOMOPOULOS, Alessandro PRIGIONE, Zoltan IVICS, Šárka POSPÍŠILOVÁ, Petr SKLÁDAL, Zsuzsanna IZSVAK, Miguel A. ANDRADE-NAVARRO a Spyros PETRAKIS. Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery. Redox Biology. Amsterdam: Elsevier, 2020, roč. 32, MAY 2020, s. 1-16. ISSN 2213-2317. Dostupné z: https://dx.doi.org/10.1016/j.redox.2020.101458.

@article{1689437,
   author = {Laidou, Stamatia and AlanisandLobato, Gregorio and Přibyl, Jan and Raskó, Tamás and Tichý, Boris and Mikulášek, Kamil and Tsagiopoulou, Maria and Oppelt, Jan and Kastrinaki, Georgia and Lefaki, Maria and Singh, Manvendra and Zink, Annika and Chondrogianni, Niki and Psomopoulos, Fotis and Prigione, Alessandro and Ivics, Zoltan and Pospíšilová, Šárka and Skládal, Petr and Izsvak, Zsuzsanna and AndradeandNavarro, Miguel A. and Petrakis, Spyros},
   article_location = {Amsterdam},
   article_number = {MAY 2020},
   doi = {http://dx.doi.org/10.1016/j.redox.2020.101458},
   keywords = {Ataxin-1; Polyglutamine; Sleeping beauty transposon; Oxidative stress; Protein network; Ribosome},
   language = {eng},
   issn = {2213-2317},
   journal = {Redox Biology},
   title = {Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery},
   url = {https://doi.org/10.1016/j.redox.2020.101458},
   volume = {32},
   year = {2020}
}

TY  - JOUR
ID  - 1689437
AU  - Laidou, Stamatia - Alanis-Lobato, Gregorio - Přibyl, Jan - Raskó, Tamás - Tichý, Boris - Mikulášek, Kamil - Tsagiopoulou, Maria - Oppelt, Jan - Kastrinaki, Georgia - Lefaki, Maria - Singh, Manvendra - Zink, Annika - Chondrogianni, Niki - Psomopoulos, Fotis - Prigione, Alessandro - Ivics, Zoltan - Pospíšilová, Šárka - Skládal, Petr - Izsvak, Zsuzsanna - Andrade-Navarro, Miguel A. - Petrakis, Spyros
PY  - 2020
TI  - Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery
JF  - Redox Biology
VL  - 32
IS  - MAY 2020
SP  - 1-16
EP  - 1-16
PB  - Elsevier
SN  - 22132317
KW  - Ataxin-1
KW  - Polyglutamine
KW  - Sleeping beauty transposon
KW  - Oxidative stress
KW  - Protein network
KW  - Ribosome
UR  - https://doi.org/10.1016/j.redox.2020.101458
L2  - https://doi.org/10.1016/j.redox.2020.101458
N2  - Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expression of the mutant protein. We characterized the structure and the protein composition of insoluble polyQ IIBs which gradually occupy the nuclei and are responsible for the generation of reactive oxygen species. In response to their formation, our transcriptome analysis reveals a cerebellum-specific perturbed protein interaction network, primarily affecting protein synthesis. We propose that insoluble polyQ IIBs cause oxidative and nucleolar stress and affect the assembly of the ribosome by capturing or down-regulating essential components. The inducible cell system can be utilized to decipher the cellular consequences of polyQ protein aggregation. Our strategy provides a broadly applicable methodology for studying polyQ diseases.
ER  -

LAIDOU, Stamatia, Gregorio ALANIS-LOBATO, Jan PŘIBYL, Tamás RASKÓ, Boris TICHÝ, Kamil MIKULÁŠEK, Maria TSAGIOPOULOU, Jan OPPELT, Georgia KASTRINAKI, Maria LEFAKI, Manvendra SINGH, Annika ZINK, Niki CHONDROGIANNI, Fotis PSOMOPOULOS, Alessandro PRIGIONE, Zoltan IVICS, Šárka POSPÍŠILOVÁ, Petr SKLÁDAL, Zsuzsanna IZSVAK, Miguel A. ANDRADE-NAVARRO a Spyros PETRAKIS. Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery. \textit{Redox Biology}. Amsterdam: Elsevier, 2020, roč.~32, MAY 2020, s.~1-16. ISSN~2213-2317. Dostupné z: https://dx.doi.org/10.1016/j.redox.2020.101458.

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