scholarly journals RNA Molecular Signature Profiling in PBMCs of Sporadic ALS Patients: HSP70 Overexpression Is Associated with Nuclear SOD1

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 293
Author(s):  
Maria Garofalo ◽  
Cecilia Pandini ◽  
Matteo Bordoni ◽  
Emanuela Jacchetti ◽  
Luca Diamanti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mononuclear Cells ◽  
Neurodegenerative Disorder ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
Molecular Signature ◽  
Protective Mechanism ◽  
Peripheral Blood Mononuclear ◽  
Sporadic Als ◽  
Als Patients

Superoxide dismutase 1 (SOD1) is one of the causative genes associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder. SOD1 aggregation contributes to ALS pathogenesis. A fraction of the protein is localized in the nucleus (nSOD1), where it seems to be involved in the regulation of genes participating in the oxidative stress response and DNA repair. Peripheral blood mononuclear cells (PBMCs) were collected from sporadic ALS (sALS) patients (n = 18) and healthy controls (n = 12) to perform RNA-sequencing experiments and differential expression analysis. Patients were stratified into groups with “high” and “low” levels of nSOD1. We obtained different gene expression patterns for high- and low-nSOD1 patients. Differentially expressed genes in high nSOD1 form a cluster similar to controls compared to the low-nSOD1 group. The pathways activated in high-nSOD1 patients are related to the upregulation of HSP70 molecular chaperones. We demonstrated that, in this condition, the DNA damage is reduced, even under oxidative stress conditions. Our findings highlight the importance of the nuclear localization of SOD1 as a protective mechanism in sALS patients.

scholarly journals Exercise-Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ypatios Spanidis ◽  
Aristidis S. Veskoukis ◽  
Christina Papanikolaou ◽  
Dimitrios Stagos ◽  
Alexandros Priftis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Eccentric Exercise ◽  
Mononuclear Cells ◽  
Reductive Group ◽  
Redox Status ◽  
Protective Mechanism ◽  
Peripheral Blood Mononuclear ◽  
Reductive Stress ◽  
Blood Mononuclear Cells ◽  
Baseline Values

Eccentric exercise is a well-studied modality that induces oxidative stress and muscle damage. Furthermore, it promotes inflammatory response in which peripheral blood mononuclear cells (PBMCs) are the major mediators. Although free radicals are necessary in a specific range of concentrations, yet unknown, it remains unclear whether reductive redox status (i.e., increased antioxidant defenses and impaired free radical generation) is beneficial or not. Thus, the aim of the present investigation was to examine the effects of reductive stress and the impact of reduced glutathione (GSH) baseline values on the ability of PBMCs to counteract oxidative stress induced by a potent oxidative agent. PBMCs were isolated from the blood of subjects who performed eccentric exercise and treated with t-BOOH for 24 h. The subjects were clustered in the reductive and the oxidative group on the basis of increased or decreased GSH concentration postexercise compared to preexercise values, respectively. According to our results in PBMCs, lipid peroxidation levels as depicted by thiobarbituric acid reactive substances (TBARS) remained unchanged in the reductive group contrary to the observed enhancement in the oxidative group. In addition, GSH concentration and catalase activity increased in the reductive group, whereas they were not affected in the oxidative group. In conclusion, the effects of an oxidizing agent on the redox status of PBMCs isolated from the blood of athletes after acute eccentric exercise are dependent on the baseline values of GSH in erythrocytes. Otherwise, reductive stress defined by increased GSH levels is a protective mechanism, at least when followed by an oxidative stimulus.

scholarly journals Identification of Circulating Gene Expression Signatures of Intracranial Aneurysm in Peripheral Blood Mononuclear Cells

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1092
Author(s):  
Vincent M. Tutino ◽  
Haley R. Zebraski ◽  
Hamidreza Rajabzadeh-Oghaz ◽  
Muhammad Waqas ◽  
James N. Jarvis ◽  
...  
Keyword(s):  
Intracranial Aneurysm ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Intracellular Signaling ◽  
Mononuclear Cells ◽  
Differential Expression Analysis ◽  
Validation Dataset ◽  
Cytokine Signaling ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMCs) play an important role in the inflammation that accompanies intracranial aneurysm (IA) pathophysiology. We hypothesized that PBMCs have different transcriptional profiles in patients harboring IAs as compared to IA-free controls, which could be the basis for potential blood-based biomarkers for the disease. To test this, we isolated PBMC RNA from whole blood of 52 subjects (24 with IA, 28 without) and performed next-generation RNA sequencing to obtain their transcriptomes. In a randomly assigned discovery cohort of n = 39 patients, we performed differential expression analysis to define an IA-associated signature of 54 genes (q < 0.05 and an absolute fold-change ≥ 1.3). In the withheld validation dataset, these genes could delineate patients with IAs from controls, as the majority of them still had the same direction of expression difference. Bioinformatics analyses by gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA) demonstrated enrichment of structural regulation processes, intracellular signaling function, regulation of ion transport, and cell adhesion. IPA analysis showed that these processes were likely coordinated through NF-kB, cytokine signaling, growth factors, and TNF activity. Correlation analysis with aneurysm size and risk assessment metrics showed that 4/54 genes were associated with rupture risk. These findings highlight the potential to develop predictive biomarkers from PBMCs to identify patients harboring IAs.

scholarly journals Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients

2009 ◽  
Vol 38 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Claudia Cappuzzello ◽  
Monica Napolitano ◽  
Diego Arcelli ◽  
Guido Melillo ◽  
Roberta Melchionna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Chemokine Receptor ◽  
Expression Profiling ◽  
Mononuclear Cells ◽  
Molecular Signature ◽  
Peripheral Blood Mononuclear ◽  
Control Subjects ◽  
Blood Mononuclear Cells

The present study was aimed at identifying chronic heart failure (CHF) biomarkers from peripheral blood mononuclear cells (PBMCs) in patients with ischemic (ICM) and nonischemic dilated (NIDCM) cardiomyopathy. PBMC gene expression profiling was performed by Affymetrix in two patient groups, 1) ICM ( n = 12) and 2) NIDCM ( n = 12) New York Heart Association (NYHA) III/IV CHF patients, vs. 3) age- and sex-matched control subjects ( n = 12). Extracted RNAs were then pooled and hybridized to a total of 11 microarrays. Gene ontology (GO) analysis separated gene profiling into functional classes. Prediction analysis of microarrays (PAM) and significance analysis of microarrays (SAM) were utilized in order to identify a molecular signature. Candidate markers were validated by quantitative real-time polymerase chain reaction. We identified a gene expression profiling that distinguished between CHF patients and control subjects. Interestingly, among the set of genes constituting the signature, chemokine receptor (CCR2, CX3CR1) and early growth response (EGR1, 2, 3) family members were found to be upregulated in CHF patients vs. control subjects and to be part of a gene network. Such findings were strengthened by the analysis of an additional 26 CHF patients ( n = 14 ICM and n = 12 NIDCM), which yielded similar results. The present study represents the first large-scale gene expression analysis of CHF patient PBMCs that identified a molecular signature of CHF and putative biomarkers of CHF, i.e., chemokine receptor and EGR family members. Furthermore, EGR1 expression levels can discriminate between ICM and NIDCM CHF patients.

scholarly journals Nuclear Phospho-SOD1 Protects DNA from Oxidative Stress Damage in Amyotrophic Lateral Sclerosis

2019 ◽  
Vol 8 (5) ◽  
pp. 729 ◽  
Author(s):  
Matteo Bordoni ◽  
Orietta Pansarasa ◽  
Michela Dell’Orco ◽  
Valeria Crippa ◽  
Stella Gagliardi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Amyotrophic Lateral Sclerosis ◽  
Oxidative Damage ◽  
Motor Neurons ◽  
Mononuclear Cells ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Peripheral Blood Mononuclear ◽  
High Level ◽  
Lateral Sclerosis

We already demonstrated that in peripheral blood mononuclear cells (PBMCs) of sporadic amyotrophic lateral sclerosis (sALS) patients, superoxide dismutase 1 (SOD1) was present in an aggregated form in the cytoplasmic compartment. Here, we investigated the possible effect of soluble SOD1 decrease and its consequent aggregation. We found an increase in DNA damage in patients PBMCs characterized by a high level of aggregated SOD1, while we found no DNA damage in PBMCs with normal soluble SOD1. We found an activation of ataxia-telangiectasia-mutated (ATM)/Chk2 and ATM and Rad3-related (ATR)/Chk1 DNA damage response pathways, which lead to phosphorylation of SOD1. Moreover, data showed that phosphorylation allows SOD1 to shift from the cytoplasm to the nucleus, protecting DNA from oxidative damage. Such pathway was finally confirmed in our cellular model. Our data lead us to suppose that in a sub-group of patients this physiologic pathway is non-functional, leading to an accumulation of DNA damage that causes the death of particularly susceptible cells, like motor neurons. In conclusion, during oxidative stress SOD1 is phosphorylated by Chk2 leading to its translocation in the nuclear compartment, in which SOD1 protects DNA from oxidative damage. This pathway, inefficient in sALS patients, could represent an innovative therapeutic target.

scholarly journals Metabolic Syndrome Is Associated with Oxidative Stress and Proinflammatory State

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 236 ◽  
Author(s):  
Margalida Monserrat-Mesquida ◽  
Magdalena Quetglas-Llabrés ◽  
Xavier Capó ◽  
Cristina Bouzas ◽  
David Mateos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Mononuclear Cells ◽  
Antioxidant Defenses ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Inflammatory Parameters ◽  
Increased Risk ◽  
Factor Α

Metabolic syndrome (MetS) is associated with increased risk of developing diabetes and cardiovascular diseases. MetS is also characterized by an increase of oxidative stress which contributes to impaired inflammation, vascular function, and atherosclerosis. The aim was to assess the oxidative stress and inflammatory markers in plasma and PBMCs in adults with or without MetS. Antioxidant and inflammatory parameters were measured in peripheral blood mononuclear cells (PBMCs) of 80 men and 80 women over 55 to 80-years-old residing in the Balearic Islands without previously documented cardiovascular disease. Circulating leukocytes, neutrophils, lymphocytes, basophils, and monocytes were higher in MetS subjects with respect to those without MetS. Plasma levels of malondialdehyde, tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) levels were higher in MetS subjects in both genders, but the superoxide dismutase activity was lower. The myeloperoxidase plasma activity was higher in the MetS male subjects. Higher activities and protein levels of catalase and glutathione reductase in PBMCs were observed in MetS subjects in both genders. Obtained data show that MetS is associated with oxidative stress and a proinflammatory state and with high antioxidant defenses in PBMCs probably derived from a pre-activation state of immune cells.

scholarly journals Identification of IFITM1 and IFITM3 in Goose: Gene Structure, Expression Patterns, and Immune Reponses against Tembusu Virus Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Anqi Wang ◽  
Lipei Sun ◽  
Mingshu Wang ◽  
Renyong Jia ◽  
Dekang Zhu ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Expression Patterns ◽  
Harderian Gland ◽  
Bursa Of Fabricius ◽  
Poly I:C ◽  
Peripheral Blood Mononuclear ◽  
Interferon Stimulated Genes ◽  
Cecal Tonsil ◽  
Tembusu Virus ◽  
First Time

As interferon-stimulated genes (ISGs), interferon-inducible transmembrane proteins 1 and 3 (IFITM1 and IFITM3) can effectively inhibit the replication of multiple viruses. Here, goose IFITM1 and IFITM3 were cloned and identified for the first time. The two proteins share the same topological structure and several important sites critical for the antiviral functions in other species are conserved in the goose. Goose IFITM1 and IFITM3 are most closely related to their respective orthologs in ducks; these proteins exhibited high mRNA transcript levels in immune-related tissues, including the thymus, bursa of Fabricius, and Harderian gland, compared to other tissues. Moreover, goose IFITM1 was highly constitutively expressed in gastrointestinal tract tissues, while goose IFITM3 was expressed in respiratory organs. Furthermore, goose IFITM3 was activated in goose peripheral blood mononuclear cells (PBMCs) infected with Tembusu virus (TMUV) or treated with Toll-like receptors (TLRs) agonists, while only the R848 and Poly (I:C) agonists induced significant upregulation of goose IFITM1. Furthermore, goose IFITM1 and IFITM3 were upregulated in the sampled tissues, to some extent, after TMUV infection. Notably, significant upregulation of goose IFITM1 and IFITM3 was detected in the cecum and cecal tonsil, where TMUV was primarily distributed. These data provide new insights into the immune effectors in geese and promote our understanding of the role of IFITM1 and IFITM3 in the defense against TMUV.

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