Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y

Up-regulated Gene clone 7 (URG7) is a protein localized in the endoplasmic reticulum (ER) and overexpressed in liver cells upon hepatitis B virus (HBV) infection. Its activity has been related to the attenuation of ER stress resulting from HBV infection, promoting protein folding and ubiquitination and reducing cell apoptosis overall. While the antiapoptotic activity of URG7 in HBV-infected cells may have negative implications, this effect could be exploited positively in the field of proteinopathies, such as neurodegenerative diseases. In this work, we aimed to verify the possible contribution of URG7 as a reliever of cellular proteostasis alterations in a neuronal in vitro system. Following tunicamycin-induced ER stress, URG7 was shown to modulate different markers of the unfolded protein response (UPR) in favor of cell survival, mitigating ER stress and activating autophagy. Furthermore, URG7 promoted ubiquitination, and determined a reduction in protein aggregation, calcium release from the ER and intracellular ROS content, confirming its pro-survival activity. Therefore, in light of the results reported in this work, we hypothesize that URG7 offers activity as an ER stress reliever in a neuronal in vitro model, and we paved the way for a new approach in the treatment of neurodegenerative diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

International journal of molecular sciences - 25(2023), 1 vom: 29. Dez.

Sprache:

Englisch

Beteiligte Personen:

Nigro, Ilaria [VerfasserIn]
Miglionico, Rocchina [VerfasserIn]
Carmosino, Monica [VerfasserIn]
Gerbino, Andrea [VerfasserIn]
Masato, Anna [VerfasserIn]
Sandre, Michele [VerfasserIn]
Bubacco, Luigi [VerfasserIn]
Antonini, Angelo [VerfasserIn]
Rinaldi, Roberta [VerfasserIn]
Bisaccia, Faustino [VerfasserIn]
Armentano, Maria Francesca [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis
Autophagy
Endoplasmic reticulum (ER) stress
Journal Article
Neurodegeneration
Neuroprotective Agents
PI3K/AKT pathway
Protein misfolding
Tunicamycin
Unfolded protein response (UPR)

Anmerkungen:

Date Completed 12.01.2024

Date Revised 13.01.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms25010481

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366942344