Impact of ER stress and its reversion via chemical chaperones, on age- and proteostasis-associated pathways

• Main Author: Resende, Daniel Marcos da Silva
• Publication Date: 2019
• Format: Master thesis
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10773/28430
• topic: ER Stress; Proteostasis; Unfolded Protein Response; Aging; PERK; IRE1; ATF6; BAG3; ATF4; ERK; Calreticulin; GRP78

Aging remains to this day one of the unresolved biology areas of upmost importance and many age-related diseases are on the rise worldwide. One of aging major hallmarks, proteostasis, has several associated pathways across different segments which have not yet been fully detailed in various cell lines and are needed to better understand the underlying aging problem. Here, using a neuronal-like cell line such as SH-SY5Y, several ER stress biomarkers and proteostasis associated targets are evaluated under ER stress-induced environment through tunicamycin (TUN) or thapsigargin (TG) presence. The inclusion of neuroprotective agents such as TUDCA and homegrown compounds (HA compounds) were also included to better evaluate successful chemical reversion of ER stress and protein aggregation through target proteins. BAG3, ATF4, Calreticulin and pERK1/2 were some of the proteins included in this report as biomarkers for ER stress induction using protein or gene expression level analysis. ER stress was effectively induced with thapsigargin or tunicamycin across all target proteins. ATF4, calreticulin and pERK1/2 protein and/or gene expression values decreased after neuroprotective agents’ treatment. However, no ER stress reversion was achieved for GRP78 and BAG3. XBP1s achieved positive results only for tunicamycin-treated conditions. Overall, ER stress induction was partially or totally reverted with success by TUDCA and HA compounds in SH-SY5Y.