DJ-1-Nrf2 axis is activated upon murine β-coronavirus infection in the CNS

Abstract

Coronaviruses have emerged as alarming pathogens owing to their inherent ability of genetic variation and cross-species transmission. Coronavirus infection burdens the endoplasmic reticulum (ER.), causes reactive oxygen species production and induces host stress responses, including unfolded protein response (UPR) and antioxidant system. In this study, we have employed a neurotropic murine β-coronavirus (M-CoV) infection in the Central Nervous System (CNS) of experimental mice model to study the role of host stress responses mediated by an interplay of DJ-1 and XBP1. DJ-1 is an antioxidant molecule with established functions in neurodegeneration. However, its regulation in virus-induced cellular stress response is less explored. Our study showed that M-CoV infection activated the glial cells and induced antioxidant and UPR genes during the acute stage when the viral titer peaks. As the virus particles decreased and acute neuroinflammation diminished at day ten p.i., a significant upregulation in UPR responsive XBP1, antioxidant DJ-1, and downstream signaling molecules, including Nrf2, was recorded in the brain tissues. Additionally, preliminary in silico analysis of the binding between the DJ-1 promoter and a positively charged groove of XBP1 is also investigated, thus hinting at a mechanism behind the upregulation of DJ-1 during MHV-infection. The current study thus attempts to elucidate a novel interplay between the antioxidant system and UPR in the outcome of coronavirus infection.

The antioxidant effect of tetrahedral framework nucleic acid‐based delivery of small activating RNA targeting DJ‐1 on retinal oxidative stress injury

“…Studies have reported that DJ‐1 can mediate cell survival by activating the extracellular signal‐regulated kinase (Erk) pathway and the downstream nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway. 30 , 31 Our western blotting results also showed that the phosphorylation of Erk1/2 and its downstream transcription factor Elk‐1 was upregulated by 250 nM tFNAs‐DJ‐1‐saRNA in H 2 O 2 ‐treated HUVECs (Figure 5D ). On the other hand, 125 nM tFNAs‐DJ‐1‐saRNA could also efficiently promote the expression of the phosphorylation of Akt, Nrf2, and heme oxygenase‐1 (HO‐1) in ARPE‐19 cells (Figure 5E ).…”

“…Studies have reported that DJ-1 can mediate cell survival by activating the extracellular signal-regulated kinase (Erk) pathway and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. 30,31 Our western blotting results also showed that the phosphorylation of Erk1/2 and its downstream transcription factor Elk-1 was upregulated by 250 nM tFNAs-DJ-1-saRNA in H 2 O 2 -treated HUVECs (Figure 5D).…”

Elucidating the Role of a Shared lncRNA-miRNA-mRNA Network in Exacerbating Parkinson’s Disease Symptoms in the Context of COVID-19 Infection

“…They also demonstrated that the alteration of DJ-1, an oxidant-sensing molecule, was the first instance in M-CoV. 94 Therefore, Enrichr results of the GDS1028 dataset showed higher expression levels of SNCA and PARK7 in the PBMCs of patients with SARS (COVID-19) compared to healthy individuals. It could be argued that the parallel expression of these genes in PD and COVID-19 would probably lead to an increase in PD symptoms due to infection with COVID-19.…”