Endoplasmic Reticulum Stress Markers and Their Possible Implications in Leprosy’s Pathogenesis

Hirai, Kelly Emi; Sousa, Jorge Rodrigues de; Silva, Luciana Mota; Dias, Leônidas Braga; Furlaneto, Ismari Perini; Carneiro, Francisca Regina Oliveira; Aarão, Tinara Leila de Souza; Sotto, Mírian Nacagami; Quaresma, Juarez Antônio Simões

doi:10.1155/2018/7067961

Cited by 13 publications

(9 citation statements)

References 50 publications

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“…PERK staining was observed in cellular nuclei in all groups of mice, an immunohistochemical pattern described for this protein in other studies [ 43 ] ( Figure 1 A). Clinical TgU1 + /TgVole + mice showed an upregulation of PERK in the thalamus and hypothalamus compared to their TgU1 + /TgVole − controls, which presented faint PERK immunolabeling in these regions.…”

Section: Resultssupporting

confidence: 83%

Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease

Otero

Betancor

Eraña

et al. 2021

IJMS

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Prion diseases are a group of neurodegenerative disorders that can be spontaneous, familial or acquired by infection. The conversion of the prion protein PrPC to its abnormal and misfolded isoform PrPSc is the main event in the pathogenesis of prion diseases of all origins. In spontaneous prion diseases, the mechanisms that trigger the formation of PrPSc in the central nervous system remain unknown. Several reports have demonstrated that the accumulation of PrPSc can induce endoplasmic reticulum (ER) stress and proteasome impairment from the early stages of the prion disease. Both mechanisms lead to an increment of PrP aggregates in the secretory pathway, which could explain the pathogenesis of spontaneous prion diseases. Here, we investigate the role of ER stress and proteasome impairment during prion disorders in a murine model of spontaneous prion disease (TgVole) co-expressing the UbG76V-GFP reporter, which allows measuring the proteasome activity in vivo. Spontaneously prion-affected mice showed a significantly higher accumulation of the PKR-like ER kinase (PERK), the ER chaperone binding immunoglobulin protein (BiP/Grp78), the ER protein disulfide isomerase (PDI) and the UbG76V-GFP reporter than age-matched controls in certain brain areas. The upregulation of PERK, BiP, PDI and ubiquitin was detected from the preclinical stage of the disease, indicating that ER stress and proteasome impairment begin at early stages of the spontaneous disease. Strong correlations were found between the deposition of these markers and neuropathological markers of prion disease in both preclinical and clinical mice. Our results suggest that both ER stress and proteasome impairment occur during the pathogenesis of spontaneous prion diseases.

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Section: Resultssupporting

confidence: 83%

Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease

Otero

Betancor

Eraña

et al. 2021

IJMS

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“…The two-component signal transduction system BarA-UvrY regulates metabolism, motility, BF, stress resistance, virulence, and QS in CM pathogens by activating the transcription of genes for regulatory small RNAs (Zere et al, 2015). The up-regulation of genes coding for proteolytic activity, grp78 during hostpathogen interactions in CM, is associated with endoplasmic reticulum (ER) stress which further triggers proteolytic activities to initiate the mechanism of pathogenesis and cell death (Hirai et al, 2018). Catalase activity is a marker of bovine mastitis, which plays a central role in milk redox control and markedly increases during the pathophysiology of bovine CM (Andrei et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Insights Into the Resistome of Bovine Clinical Mastitis Microbiome, a Key Factor in Disease Complication

et al. 2020

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Bovine clinical mastitis (CM) is one of the most prevalent diseases caused by a wide range of resident microbes. The emergence of antimicrobial resistance in CM bacteria is well-known, however, the genomic resistance composition (the resistome) at the microbiome-level is not well characterized. In this study, we applied whole metagenome sequencing (WMS) to characterize the resistome of the CM microbiome, focusing on antibiotics and metals resistance, biofilm formation (BF), and quorum sensing (QS) along with in vitro resistance assays of six selected pathogens isolated from the same CM samples. The WMS generated an average of 21.13 million reads (post-processing) from 25 CM samples that mapped to 519 bacterial strains, of which 30.06% were previously unreported. We found a significant (P = 0.001) association between the resistomes and microbiome composition with no association with cattle breed, despite significant differences in microbiome diversity among breeds. The in vitro investigation determined that 76.2% of six selected pathogens considered "biofilm formers" actually formed biofilms and were also highly resistant to tetracycline, doxycycline, nalidixic acid, ampicillin, and chloramphenicol and remained sensitive to metals (Cr, Co, Ni, Cu, Zn) at varying concentrations. We also found bacterial flagellar movement and chemotaxis, regulation and cell signaling, and oxidative stress to be significantly associated with the pathophysiology of CM. Thus, identifying CM microbiomes, and analyzing their resistomes and genomic potentials will help improve the optimization of therapeutic schemes involving antibiotics and/or metals usage in the prevention and control of bovine CM.

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“…Endoplasmic reticulum (ER) stress contributes to respiratory disease pathogenesis and plays an important role in inducing lung inflammation [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. To investigate whether DEP exposure is associated with ER stress in our murine model of DEP-induced neutrophilic lung inflammation, we used Western blotting to measure the BiP and CHOP protein expression in lung tissues of DEP-treated mice.…”

Section: Resultsmentioning

confidence: 99%

“…When ER stress is detected, bound immunoglobulin protein (BiP) dissociates from the ER-transmembrane stress sensors PKR-like eukaryotic initiation factor 2a kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) to restore ER homeostasis. However, when these attempts to recover equilibrium fail, programmed cell death is initiated via CCAAT/enhancer binding to protein-homologous protein (CHOP) upregulation [ 17 ]. Several studies have demonstrated that ER stress influences the development and progression of respiratory diseases such as asthma, fibrosis, and acute lung injury [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages

et al. 2020

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Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 μg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.

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Endoplasmic Reticulum Stress Markers and Their Possible Implications in Leprosy’s Pathogenesis

Cited by 13 publications

References 50 publications

Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease

Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease

Insights Into the Resistome of Bovine Clinical Mastitis Microbiome, a Key Factor in Disease Complication

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages

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