Lack of the Histone Deacetylase SIRT1 Leads to Protection against Endoplasmic Reticulum Stress through the Upregulation of Heat Shock Proteins
Latorre, Jessica (Institute for Biomedical Research of Barcelona (Barcelona))
de Vera, Núria (Institute for Biomedical Research of Barcelona (Barcelona))
Santalucía, Tomàs (Universitat de Barcelona)
Balada Caballé, Rafael (Institute for Biomedical Research of Barcelona (Barcelona))
Marazuela-Duque, Anna (Chromatin Biology Laboratory. Josep Carreras Leukaemia Research Institute)
Vaquero, Alejandro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Planas, Anna M (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Petegnief, Valérie (Institut d'Investigacions Biomèdiques August Pi i Sunyer)

Fecha:	2024
Resumen:	Histone deacetylase SIRT1 represses gene expression through the deacetylation of histones and transcription factors and is involved in the protective cell response to stress and aging. However, upon endoplasmic reticulum (ER) stress, SIRT1 impairs the IRE1α branch of the unfolded protein response (UPR) through the inhibition of the transcriptional activity of XBP-1 and SIRT1 deficiency is beneficial under these conditions. We hypothesized that SIRT1 deficiency may unlock the blockade of transcription factors unrelated to the UPR promoting the synthesis of chaperones and improving the stability of immature proteins or triggering the clearance of unfolded proteins. SIRT1+/+ and SIRT1-/- fibroblasts were exposed to the ER stress inducer tunicamycin and cell survival and expression of heat shock proteins were analyzed 24 h after the treatment. We observed that SIRT1 loss significantly reduced cell sensitivity to ER stress and showed that SIRT1-/- but not SIRT1+/+ cells constitutively expressed high levels of phospho-STAT3 and heat shock proteins. Hsp70 silencing in SIRT1-/- cells abolished the resistance to ER stress. Furthermore, accumulation of ubiquitinated proteins was lower in SIRT1-/- than in SIRT1+/+ cells. Our data showed that SIRT1 deficiency enabled chaperones upregulation and boosted the proteasome activity, two processes that are beneficial for coping with ER stress.
Ayudas:	"la Caixa" Foundation 110431 Agencia Estatal de Investigación PID2020-117284RB-I0
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Sirtuin ; Hsp70 ; STAT3 ; ER stress
Publicado en:	International journal of molecular sciences, Vol. 25 Núm. 5 (march 2024) , p. 2856, ISSN 1422-0067

DOI: 10.3390/ijms25052856
PMID: 38474102

16 p, 1.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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