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QUANTITATIVE SUBCELLULAR PROTEOMICS OF THE ORBITOFRONTAL CORTEX OF SCHIZOPHRENIA PATIENTS

ABSTRACT: We analyzed orbitofrontal cortex post-mortem brain tissue from patients. We generated an organellar proteome map from different subcellular fractions such as mitochondria (MIT), crude nuclear fraction (NUC) and cytoplasm (CYT) with the aim to monitor the subproteome changes using iTRAQ labelling for relative quantification and Selected Reaction Monitoring (SRM) for targeted quantification.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Schizophrenia

SUBMITTER: Proteomics Unit

LAB HEAD: Fabio Nogueira

PROVIDER: PXD014284 | Pride | 2019-10-10

REPOSITORIES: Pride

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			Action	DRS
	Cit_281117_test2.pdResult	Other
	Mito_271117_iTRAQ.pdResult	Other
	Nucleo271117.pdResult	Other
	VL_0000628_G1_MIT_REP1.raw	Raw
	VL_0000630_G1_MIT_REP2.raw	Raw

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Publications

Quantitative Subcellular Proteomics of the Orbitofrontal Cortex of Schizophrenia Patients.

Velásquez Erika E Martins-de-Souza Daniel D Velásquez Ingrid I Carneiro Gabriel Reis Alves GRA Schmitt Andrea A Falkai Peter P Domont Gilberto B GB Nogueira Fabio C S FCS

Journal of proteome research 20191028 12

Schizophrenia is a chronic disease characterized by the impairment of mental functions with a marked social dysfunction. A quantitative proteomic approach using iTRAQ labeling and SRM, applied to the characterization of mitochondria (MIT), crude nuclear fraction (NUC), and cytoplasm (CYT), can allow the observation of dynamic changes in cell compartments providing valuable insights concerning schizophrenia physiopathology. Mass spectrometry analyses of the orbitofrontal cortex from 12 schizophre ...[more]

PMID: 31581776

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QUANTITATIVE SUBCELLULAR PROTEOMICS OF THE ORBITOFRONTAL CORTEX OF SCHIZOPHRENIA PATIENTS

Project description:We analyzed OFC post-mortem brain tissue from patients classified as residual schizophrenia according to the DMS-IV manual. In this classification, the patients do not manifest prominent positive psychotic symptoms but prevail characteristic disturbance of negative symptoms. Through the comparison of patient´s samples against a pool of control subjects without any history of psychiatric illness we generated an organellar proteome map from different subcellular fractions such as mitochondria (MIT), crude nuclear fraction (NUC) and cytoplasm (CYT) with the aim to monitor the subproteome changes using iTRAQ labelling for relative quantification and Selected Reaction Monitoring (SRM) for targeted quantification.

2019-10-07 | PXD014350 | Pride

QUANTITATIVE SUBCELLULAR PROTEOMICS OF THE ORBITOFRONTAL CORTEX OF SCHIZOPHRENIA PATIENTS

Project description:Schizophrenia is a chronic disease characterized by the impairment of mental functions with a marked social dysfunction. A proteomic approach using iTRAQ labeling and selected reaction monitoring, applied to the characterization of mitochondria (MIT), crude nuclear fraction (NUC) and cytoplasm (CYT), can allow the observation of dynamic changes in cell compartments providing valuable insights concerning schizophrenia physiopathology. Mass spectrometry analyses of the orbitofrontal cortex from 12 schizophrenia patients and 8 healthy controls identified 655 protein groups in MIT fraction, 1500 in NUC and 1591 in CYT. We found 166 groups of proteins dysregulated among all enriched cellular fractions. Through the quantitative proteomic analysis, we detect as the main biological pathways those related to calcium and glutamate imbalance, cell signaling disruption of CREB activation, axon guidance and proteins involved in the activation of NF-kB signaling along with the increase of complement proteins C3. Based on our data analysis, we suggest the activation of NF-kB as a possible pathway that links the deregulation of glutamate, calcium, apoptosis and the activation of the immune system in schizophrenia patients

2019-10-07 | PXD015356 | Pride

Diminazene aceturate (DIZE) stabilizes atherosclerotic plaques and attenuates hepatic steatosis in apolipoprotein E knockout mice by influencing macrophages polarization and taurine biosynthesis

Project description:Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are leading causes of morbidity and mortality in the Western countries. NAFLD is an important independent risk factor for the development of atherosclerosis. The renin-angiotensin system (RAS) with its two main opposing effectors: angiotensin II (Ang II) and Ang-(1-7) is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1-7) and thus favors Ang-(1-7) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator – diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE-/- mice fed a high-fat diet (HFD). We have shown that DIZE at a dose of 30 mg/kg/day given orally for 16 weeks was able to stabilize atherosclerotic lesions and attenuate hepatic steatosis in apoE-/- mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated HDL in the plasma, decreased triglycerides levels and increased biosynthesis and concentration of taurine in liver of apoE-/- mice. However, the exact molecular mechanisms of both the anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.

2021-09-09 | PXD022829 | Pride

Proteomic analysis of the liver isolated from the double (apolipoprotein E and endothelial nitric oxide synthase) knockout mice reveals decreased expression of major urinary proteins (MUPs)

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2018-03-05 | PXD006642 | Pride

Human hnRNP H1 knockdown proteomics

Project description:HNRNP1 was characterized in a multi-dimensional study involving RNAi knockdown of the protein in HeLa cells. Label-free proteomics was used to characterize protein expression changes.

2016-01-25 | PXD000895 | Pride

Proteomic analysis of mitochondria isolated from the frontal cortex and hippocampus of apolipoprotein E knockout mice treated with Alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH2)

Project description:Recently, it has been shown that mitochondrial dysfunction and oxidative stress play important roles in the pathogenesis of neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes – the end products of lipid peroxidation, is considered to exert protective function in mitochondria. The aim of our study was to use the methods of differential proteomics in concert with molecular and morphological techniques to elucidate the changes in the frontal cortex and hippocampus of apolipoprotein E knockout (apoE-/-) mice (an animal model of the early stages of Alzheimer’s disease) upon treatment with Alda-1 – a small molecular weight activator of ALDH2.

2017-02-23 | PXD004022 | Pride

PKCγ-mediated phosphorylation of CRMP2 regulates dendritic outgrowth in cerebellar Purkinje cells

Project description:The signalling protein PKCγ is a major regulator of Purkinje cell development and synaptic function. We have shown previously that increased PKCγ activity impairs dendritic development of cerebellar Purkinje cells. Mutations in the protein kinase Cγ gene (PRKCG) cause spinocerebellar ataxia type 14 (SCA14). In a transgenic mouse model of SCA14 expressing the human S361G mutation, Purkinje cell dendritic development is impaired in cerebellar slice cultures similar to pharmacological activation of PKC. The mechanisms of PKCγ-driven inhibition of dendritic growth are still unclear. Using immunoprecipitation-coupled mass spectrometry analysis we have identified Collapsin Response Mediator Protein 2 (CRMP2) as a protein interacting with constitutive active PKCγ(S361G) and confirmed the interaction with the Duolink™ proximity ligation assay. We show that in cerebellar slice cultures from PKCγ(S361G)- mice, phosphorylation of CRMP2 at the known PKC target site Thr555 is increased in Purkinje cells confirming phosphorylation of CRMP2 by PKCγ. miRNA-mediated CRMP2 knockdown decreased Purkinje cell dendritic outgrowth in dissociated cerebellar cultures as did the transfection of CRMP2 mutants with a modified Thr555 site. In contrast, dendritic development was normal after wildtype CRMP2 overexpression. In a novel knock-in mouse expressing only the phospho-defective T555A-mutant CRMP2, Purkinje cell dendritic development was reduced in dissociated cultures. This reduction could be rescued by transfecting wildtype CRMP2 but only partially by the phospho-mimetic T555D-mutant. Our findings establish CRMP2 as an important target of PKCγ phosphorylation in Purkinje cells mediating its control of dendritic development. Dynamic regulation of CRMP2 phosphorylation via PKCγ is required for its correct function.

2022-02-24 | PXD020124 | Pride

Stress hormones induce breast intra-tumor heterogeneity

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