Abstract：
:Adenovirus Delta-24-RGD has shown a remarkable efficacy in a phase I clinical trial for glioblastoma. Delta-24-RGD induces autophagy in glioma cells, however, the molecular derangements associated with Delta-24-RGD infection remains poorly understood. Here, proteomics was applied to characterize the glioma metabolic disturbances soon after Delta-24-RGD internalization and late in infection. Minutes post-infection, a rapid survival reprogramming of glioma cells was evidenced by an early c-Jun activation and a time-dependent dephosphorylation of multiple survival kinases. At 48 h post-infection (hpi), a severe intracellular proteostasis impairment was characterized, detecting differentially expressed proteins related to mRNA splicing, cytoskeletal organization, oxidative response, and inflammation. Specific kinase-regulated protein interactomes for Delta-24-RGD-modulated proteome revealed interferences with the activation dynamics of protein kinases C and A (PKC, PKA), tyrosine-protein kinase Src (c-Src), glycogen synthase kinase-3 (GSK-3) as well as serine/threonine-protein phosphatases 1 and 2A (PP1, PP2A) at 48hpi, in parallel with adenoviral protein overproduction. Moreover, the late activation of the nuclear factor kappa B (NF-κB) correlates with the extracellular increment of specific cytokines involved in migration, and activation of different inflammatory cells. Taken together, our integrative analysis provides further insights into the effects triggered by Delta-24-RGD in the modulation of tumor suppression and immune response against glioma. SIGNIFICANCE: The current study provides new insights regarding the molecular mechanisms governing the glioma metabolism during Delta-24-RGD oncolytic adenoviral therapy. The compilation and analysis of intracellular and extracellular proteomics have led us to characterize: i) the cell survival reprogramming during Delta-24-RGD internalization, ii) the proteostatic disarrangement induced by Delta-24-RGD during the autophagic stage, iii) the protein interactomes for Delta-24-RGD-modulated proteome, iv) the regulatory effects on kinase dynamics induced by Delta-24-RGD late in infection, and v) the overproduction of multitasking cytokines upon Delta-24-RGD treatment. We consider that the quantitative molecular maps generated in this study may establish the foundations for the development of complementary adenoviral based-vectors to increase the potency against glioma.
journal_name
J Proteomicsjournal_title
Journal of proteomicsauthors
González-Morales A,Zabaleta A,García-Moure M,Alonso MM,Fernández-Irigoyen J,Santamaría Edoi
10.1016/j.jprot.2018.11.020subject
Has Abstractpub_date
2019-03-01 00:00:00pages
168-178eissn
1874-3919issn
1876-7737pii
S1874-3919(18)30418-4journal_volume
194pub_type
杂志文章abstract：UNLABELLED:Plant pathogens face different environmental clues depending on the stage of the infection cycle they are in. Fusarium graminearum infects small grain cereals producing trichothecenes type B (TB) that act as virulence factor in the interaction with the plant and have important food safety implications. This ...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2015.11.010
更新日期：2016-03-30 00:00:00
abstract：:Advances in mass spectrometry technology, high-throughput proteomics and genome annotations have resulted in significant increases in our molecular understanding of sperm composition. Using improved separation and detection methods and an updated genome annotation, a re-analysis of the Drosophila melanogaster sperm pr...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2010.09.002
更新日期：2010-10-10 00:00:00
abstract：:Lysine succinylation is a newly identified protein post-translational modification (PTM) of lysine residues. Increasing evidences demonstrate that this modification is prevalent in mitochondria and regulates many vital cellular processes, especially metabolism. Here, we determined the succinylome of the silkworm (Bomb...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2017.12.019
更新日期：2018-03-01 00:00:00
abstract：:Calcium (Ca2+) controls progression through the mammalian cell cycle by engaging a diverse range of molecular pathways. While the essential role of spatio-temporal Ca2+ signalling in the cell cycle is well established, the precise mechanisms by which it regulates cell cycle entry and progression through G1 are not par...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2017.08.006
更新日期：2018-01-06 00:00:00
abstract：:The silkworm Bombyx mori is of great economic value. The B. mori nuclear polyhedrosis virus (BmNPV) is one of the most common and severe pathogens for silkworm. Although certain immune mechanisms exist in silkworms, most silkworms are still susceptible to BmNPV infection. Interestingly, BmNPV infection resistance in s...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.04.015
更新日期：2012-06-27 00:00:00
abstract：:Molecular aging of proteins results from the complex association of different reactions that lead to the progressive alteration of their structural and functional properties. These reactions, which include oxidation, glycoxidation, carbonylation and carbamylation, occur during aging and are amplified in various chroni...
journal_title：Journal of proteomics
pub_type： 杂志文章,评审
doi：10.1016/j.jprot.2013.02.015
更新日期：2013-10-30 00:00:00
abstract：:Ever since antibiotics were used to help humanity battle infectious diseases, microorganisms straight away fought back. Antibiotic resistance mechanisms indeed provide microbes with possibilities to by-pass and survive the action of antibiotic drugs. Several methods have been employed to identify these microbial resis...
journal_title：Journal of proteomics
pub_type： 杂志文章,评审
doi：10.1016/j.jprot.2013.10.027
更新日期：2014-01-31 00:00:00
abstract：:Glycoproteins play pivotal roles in a series of biological processes and their glycosylation patterns need to be structurally and functionally characterized. However, the lack of versatile methods to release N-glycans as functionalized forms has been undermining glycomics studies. Here a novel method is developed for ...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2018.06.002
更新日期：2018-09-15 00:00:00
abstract：UNLABELLED:There exists a growing demand in the proteomics community to standardize experimental methods and liquid chromatography-mass spectrometry (LC/MS) platforms in order to enable the acquisition of more precise and accurate quantitative data. This necessity is heightened by the evolving trend of verifying and va...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2013.07.026
更新日期：2013-12-16 00:00:00
abstract：:Proteomics is becoming more widely used as a tool in fish physiology and toxicology and can offer mechanistic insight into organism responses to environmental signals and stressors. Using a LTQ Orbitrap Velos MS/MS, we detected 1075 proteins in the reproductive testis of fathead minnow. Proteins localized to the testi...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.11.023
更新日期：2013-02-21 00:00:00
abstract：:Dystrobrevin is a dystrophin-related component of the dystrophin-associated protein complex (DAPC). Using alpha-dystrobrevin as indicator, we aimed to elucidate the interaction network of the DAPC with other proteins during apoptosis of promyelocytic HL-60 cells. The precise role(s) of DBs are not known, but we and ot...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.03.041
更新日期：2012-06-18 00:00:00
abstract：:The biological variance in protein expression of interest to biologists can only be accessed if the technical variance of the protein quantification method is low compared with the biological variance. Technical variance is dependent on the protocol employed within a quantitative proteomics experiment and accumulated ...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.09.020
更新日期：2012-12-21 00:00:00
abstract：:Tissues hypoxia caused by hemorrhage is a common complication in many clinical diseases. However, its pathological mechanism remains largely unknown. To partly address this issue, an ischemic-hypoxic rat model was established and the plasma proteomic and metabolic profiles were quantified and analyzed using TMT-based ...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2020.103924
更新日期：2020-09-30 00:00:00
abstract：:One of the important challenges for MALDI imaging mass spectrometry (MALDI-IMS) is the unambiguous identification of measured analytes. One way to do this is to match tryptic peptide MALDI-IMS m/z values with LC-MS/MS identified m/z values. Matching using current MALDI-TOF/TOF MS instruments is difficult due to the va...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.04.054
更新日期：2012-08-30 00:00:00
abstract：:The present study describes the response of a bacterial strain, isolated from a hot spring in an area with the highest levels of natural radiation, under radium ((226)Ra) stress. The bacterium has been characterized as a novel and efficient radium biosorbent and identified as a variant of Serratia marcescens by bioche...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.05.020
更新日期：2012-08-03 00:00:00
abstract：:Structural mass spectrometry with its various techniques is a powerful tool for the structural elucidation of medically relevant protein assemblies. It delivers information on the composition, stoichiometries, interactions and topologies of these assemblies. Most importantly it can deal with heterogeneous mixtures and...
journal_title：Journal of proteomics
pub_type： 杂志文章,评审
doi：10.1016/j.jprot.2017.04.019
更新日期：2018-03-20 00:00:00
abstract：:Ubiquitylation is an elaborate post-translational modification involved in all biological processes. Its pleotropic effect is driven by the ability to form complex polyubiquitin chain architectures that can influence biological functions. In this study, we optimised sample preparation and chromatographic separation of...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2020.103963
更新日期：2020-10-30 00:00:00
abstract：:Proteins in milk have wide range of functions, they are carriers of minerals or chemically vulnerable and insoluble vitamins and other compounds, stabilisers of large aggregates or micelles of lipids, and components of both innate and acquired immune defence systems. Together with other components of milk, proteins ma...
journal_title：Journal of proteomics
pub_type： 杂志文章,评审
doi：10.1016/j.jprot.2013.04.008
更新日期：2013-08-02 00:00:00
abstract：:Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen in the world. To identify new vaccine candidates a protein microarray was constructed by expressing the open reading frames (ORFs) from Chlamydia mouse pneumonitis (MoPn). C57BL/6, C3H/HeN and BALB/c mice were immunized either intranasall...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.08.017
更新日期：2012-12-21 00:00:00
abstract：UNLABELLED:Male infertility of cattleyak due to spermatogenic arrest greatly restricts their effective utilization in yak breeding. Although much work has been done to investigate the mechanisms of spermatogenic arrest, there is no information regarding the differences of protein composition between cattleyak and yak t...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2016.04.049
更新日期：2016-06-16 00:00:00
abstract：UNLABELLED:Venoms of the viperid sister genera Eristicophis and Pseudocerastes are poorly studied despite their anecdotal reputation for producing severe or even lethal envenomations. This is due in part to the remote and politically unstable regions that they occupy. All species contained are sit and wait ambush feede...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2014.09.003
更新日期：2015-02-26 00:00:00
abstract：UNLABELLED:Quantification of the antigens hemagglutinin and neuraminidase in influenza vaccines has been reported using an antibody-free liquid chromatography-mass spectrometry (LC-MS) based method known as MS(E) "Hi3". This approach is based on the average signal intensity of the three most intense tryptic peptides re...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2016.06.024
更新日期：2016-09-02 00:00:00
abstract：:There is a wide range of pathological conditions proved to be associated with inflammation. The inflammatory process offers protection against harmful stimuli such as induced cell injury and tissues damage by means of specialized mediators and cells. Alarmins, also known as endogenous danger signals or damage-associat...
journal_title：Journal of proteomics
pub_type： 杂志文章,评审
doi：10.1016/j.jprot.2016.11.006
更新日期：2017-02-05 00:00:00
abstract：:A large series of protein pathway components have been shown to be dysregulated in Down syndrome (DS) brain. No information about pathomechanisms linked to the trisomic state can be obtained from adult DS brain, however, as neurodegeneration occurs from the fourth decade. The aim of the study was to search for protein...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2011.01.009
更新日期：2011-04-01 00:00:00
abstract：:Mild olfactory dysfunction has been observed in frontotemporal dementias (FTD). However, the underlying molecular mechanisms associated to this deficit are poorly understood. We applied quantitative proteomics to analyze pathological effects on the olfactory bulb (OB) from progressive supranuclear palsy (PSP) and fron...
journal_title：Journal of proteomics
pub_type： 临床试验,杂志文章
doi：10.1016/j.jprot.2019.04.011
更新日期：2019-06-15 00:00:00
abstract：:In this study, we performed an integrated physiological and chloroplast proteome analysis of wheat seedling leaves under salt and osmotic stresses by label-free based quantitative proteomic approach. Both salt and osmotic stresses significantly increased the levels of abscisic acid and methyl jasmonate and led to dama...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2020.104097
更新日期：2021-03-15 00:00:00
abstract：:Aldosterone (Aldo) could induce cardiac fibrosis, a hallmark of heart disease. Aldo direct effects on collagen production in cardiac fibroblasts remain controversial. Our aim is to characterize changes in the proteome of adult human cardiac fibroblasts treated with Aldo to identify new proteins altered that might be n...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2017.07.011
更新日期：2017-08-23 00:00:00
abstract：:High content omic techniques in combination with stable human in vitro cell culture systems have the potential to improve on current pre-clinical safety regimes by providing detailed mechanistic information of altered cellular processes. Here we investigated the added benefit of integrating transcriptomics, proteomics...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2012.11.022
更新日期：2013-02-21 00:00:00
abstract：BACKGROUND:Oral leukoplakia is the most common potentially malignant disorder in the oral cavity and can precede carcinoma. This study aimed to identify possible oral leukoplakia salivary biomarkers. METHODS:Unstimulated saliva was collected from participants and protein concentration was determined. Proteins were the...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2016.07.029
更新日期：2017-01-16 00:00:00
abstract：UNLABELLED:Water stress (WS) predisposes peanut plants to fungal infection resulting in pre-harvest aflatoxin contamination. Major changes during water stress including oxidative stress, lead to destruction of photosynthetic apparatus and other macromolecules within cells. Two peanut cultivars with diverse drought tole...
journal_title：Journal of proteomics
pub_type： 杂志文章
doi：10.1016/j.jprot.2016.05.031
更新日期：2016-06-30 00:00:00
