Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain

Pasquale, Valeria De; Costanzo, Michele; Siciliano, Roberta; Mazzeo, Maria Fiorella; Pistorio, Valeria; Bianchi, Laura; Marchese, Emanuela; Ruoppolo, Margherita; Pavone, Luigi Michele; Caterino, Marianna

doi:10.3390/biom10030355

Cited by 32 publications

(30 citation statements)

References 103 publications

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“…Thus, serum levels of phenylalanine showed augmentation in such patients as a result of the activation of the immune response, also magnifying inflammation processes [45][46][47]. The activation of the immune response and inflammation is observed also in other diseases or models of metabolic disorders showing impairment of amino acid metabolism, in which cytokines' release is strictly regulated by the inflammasome [48][49][50]. In addition, being succinic acid, an innate immune signaling molecule during inflammation in macrophages, its increase may enhance the cytokine production during the cytokine storm syndrome that affects COVID-19 patients [18].…”

Section: Discussionmentioning

confidence: 98%

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

Caterino

Costanzo

Fedele

et al. 2021

IJMS

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COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

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Section: Discussionmentioning

confidence: 98%

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

Caterino

Costanzo

Fedele

et al. 2021

IJMS

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“…The functional profiling of a set of proteins common to the four analyzed conditions was obtained using g:Profiler software [ 52 , 53 ]. The enrichment of Gene Ontology (GO) Biological Process (BP) terms for each regulated proteome was performed using STRING [ 54 , 55 , 56 ]. The long lists of GO-BPs obtained from STRING were reduced and summarized using the REViGO software, with the final selection of the significant non-redundant BP terms [ 57 , 58 ].…”

Section: Methodsmentioning

confidence: 99%

Proteomic and Bioinformatic Investigation of Altered Pathways in Neuroglobin-Deficient Breast Cancer Cells

et al. 2021

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Neuroglobin (NGB) is a myoglobin-like monomeric globin that is involved in several processes, displaying a pivotal redox-dependent protective role in neuronal and extra-neuronal cells. NGB remarkably exerts its function upon upregulation by NGB inducers, such as 17β-estradiol (E2) and H2O2. However, the molecular bases of NGB’s functions remain undefined, mainly in non-neuronal cancer cells. Human MCF-7 breast cancer cells with a knocked-out (KO) NGB gene obtained using CRISPR/Cas9 technology were analyzed using shotgun label-free quantitative proteomics in comparison with control cells. The differential proteomics experiments were also performed after treatment with E2, H2O2, and E2 + H2O2. All the runs acquired using liquid chromatography–tandem mass spectrometry were elaborated within the same MaxQuant analysis, leading to the quantification of 1872 proteins in the global proteomic dataset. Then, a differentially regulated protein dataset was obtained for each specific treatment. After the proteomic study, multiple bioinformatics analyses were performed to highlight unbalanced pathways and processes. Here, we report the proteomic and bioinformatic investigations concerning the effects on cellular processes of NGB deficiency and cell treatments. Globally, the main processes that were affected were related to the response to stress, cytoskeleton dynamics, apoptosis, and mitochondria-driven pathways.

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“…The STRING (Search Tool for the Retrieval of Interacting Genes) online version 11 (STRING CONSORTIUM 2020) [60,61] was used for the generation of the interacting network of mitochondrial proteins. A minimum of the required interaction score of 0.150 (low confidence) was set.…”

Section: Bioinformatic Analysesmentioning

confidence: 99%

Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress

Costanzo

Caterino

Cevenini

et al. 2020

IJMS

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Methylmalonic acidemia (MMA) is a rare inborn error of metabolism caused by deficiency of the methylmalonyl-CoA mutase (MUT) enzyme. Downstream MUT deficiency, methylmalonic acid accumulates together with toxic metabolites from propionyl-CoA and other compounds upstream of the block in the enzyme pathway. The presentation is with life-threatening acidosis, respiratory distress, brain disturbance, hyperammonemia, and ketosis. Survivors develop poorly understood multi-organ damage, notably to the brain and kidneys. The HEK 293 cell line was engineered by CRISPR/Cas9 technology to knock out the MUT gene (MUT-KO). Shotgun label-free quantitative proteomics and bioinformatics analyses revealed potential damaging biological processes in MUT-deficient cells. MUT-KO induced alteration of cellular architecture and morphology, and ROS overproduction. We found the alteration of proteins involved in cytoskeleton and cell adhesion organization, cell trafficking, mitochondrial, and oxidative processes, as validated by the regulation of VIM, EXT2, SDC2, FN1, GLUL, and CHD1. Additionally, a cell model of MUT-rescuing was developed in order to control the specificity of MUT-KO effects. Globally, the proteomic landscape of MUT-KO suggests the cell model to have an increased susceptibility to propionate- and H2O2-induced stress through an impairment of the mitochondrial functionality and unbalances in the oxidation-reduction processes.

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Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain

Cited by 32 publications

References 103 publications

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

Proteomic and Bioinformatic Investigation of Altered Pathways in Neuroglobin-Deficient Breast Cancer Cells

Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress

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