scholarly journals Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys

2019 ◽  
Author(s):  
Shu Meng ◽  
Wenchao Xia ◽  
Meng Pan ◽  
Yangjie Jia ◽  
Zhanlong He ◽  
...  

Abstract Background: Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive research has been carried out on the characteristics of human hippocampal aging, there is still very little scientific understanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics profiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high throughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged 6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinformatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (the ratios of 20-y vs. 6-y, ≥1.20 or ≤ 0.83). Results: In total, 3,260 proteins were identified with a high level of confidence in rhesus hippocampus. We found 367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we found these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal adhesion-PI3K-AKT-mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeXchange with identifier PXD011398. Conclusion: This study provides a detail description of the proteomics profile related to rhesus hippocampal aging. These findings should make an important contribution to further mechanistic studies, marker selection and drug development for the prevention and treatment of aging or age-related neurodegeneration.

2019 ◽  
Author(s):  
Shu Meng ◽  
Wenchao Xia ◽  
Meng Pan ◽  
Zhanlong He ◽  
Wei Ge

Abstract Background Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive research has been carried out on the characteristics of human hippocampal aging, there is still very little scientific understanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics profiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high throughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged 6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinformatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (20-y vs. 6-y ≥1.20 or ≤ 0.83). Results In total, 3,260 proteins were identified with a high level of confidence in rhesus hippocampus. We found 367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we found these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal adhesion-PI3K-AKT-mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeXchange with identifier PXD011398. Conclusion This study provides a further understanding of the proteomics profile related to rhesus hippocampal aging, which will help to elucidate the differences between rhesus and human hippocampal aging. These findings should make an important contribution to further mechanistic studies, marker selection and drug development for the prevention and treatment of aging or age-related neurodegeneration.


2021 ◽  
Vol 22 (12) ◽  
pp. 6373
Author(s):  
Ahmad Jalloh ◽  
Antwoine Flowers ◽  
Charles Hudson ◽  
Dale Chaput ◽  
Jennifer Guergues ◽  
...  

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.


2021 ◽  
Vol 14 ◽  
Author(s):  
Changci Tong ◽  
Peifang Cong ◽  
Ying Liu ◽  
Xiuyun Shi ◽  
Lin Shi ◽  
...  

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.


Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 166 ◽  
Author(s):  
Qianqian He ◽  
Xinmei Fang ◽  
Tianhui Zhu ◽  
Shan Han ◽  
Hanmingyue Zhu ◽  
...  

Bambusa pervariabilis McClure × Dendrocalamopsis grandis (Q.H.Dai & X.l.Tao ex Keng f.) Ohrnb. blight is a widespread and dangerous forest fungus disease, and has been listed as a supplementary object of forest phytosanitary measures. In order to study the control of B. pervariabilis × D. grandis blight, this experiment was carried out. In this work, a toxin purified from the pathogen Arthrinium phaeospermum (Corda) Elli, which causes blight in B. pervariabilis × D. grandis, with homologous heterogeneity, was used as an inducer to increase resistance to B. pervariabilis × D. grandis. A functional analysis of the differentially expressed proteins after induction using a tandem mass tag labeling technique was combined with mass spectrometry and liquid chromatography mass spectrometry in order to effectively screen for the proteins related to the resistance of B. pervariabilis × D. grandis to blight. After peptide labeling, a total of 3320 unique peptides and 1791 quantitative proteins were obtained by liquid chromatography mass spectrometry analysis. Annotation and enrichment analysis of these peptides and proteins using the Gene ontology and Kyoto Encyclopedia of Genes and Genomes databases with bioinformatics software show that the differentially expressed protein functional annotation items are mainly concentrated on biological processes and cell components. Several pathways that are prominent in the Kyoto Encyclopedia of Genes and Genomes annotation and enrichment include metabolic pathways, the citrate cycle, and phenylpropanoid biosynthesis. In the Protein-protein interaction networks four differentially expressed proteins-sucrose synthase, adenosine triphosphate-citrate synthase beta chain protein 1, peroxidase, and phenylalanine ammonia-lyase significantly interact with multiple proteins and significantly enrich metabolic pathways. To verify the results of tandem mass tag, the candidate proteins were further verified by parallel reaction monitoring, and the results were consistent with the tandem mass tag data analysis results. It is confirmed that the data obtained by tandem mass tag technology are reliable. Therefore, the differentially expressed proteins and signaling pathways discovered here is the primary concern for subsequent disease resistance studies.


2019 ◽  
Vol 17 ◽  
Author(s):  
Shuang Tian ◽  
Dongjun Yang ◽  
Qian Long ◽  
Min Ling

: Mycobacterium tuberculosis (MTB) and Mycobacterium avium (MA) belong to the intracellular parasitic bacteria. To better understand how MTB survives in macrophages and the different pathogenic mechanisms of MTB and MA, the tandem mass tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used for analysis of the differentially expressed proteins in MTB-infected macrophages and MA-infected macrophages. A total of 682 proteins were found to be differentially expressed in MTB-infected cells in comparison with MA-infected cells. Gene Ontology annotation revealed the involvement of 682 differentially expressed proteins in cellular components, biological processes and molecular functions including binding, catalytic activity, metabolic processes, cellular processes, cell part, cell proliferation and apoptosis, etc. Among these, 10 proteins (O60812, P06576, O43660-2, E9PL10, O00442, M0R050, Q9H8H0, Q9BSJ8, P41240 and Q8TD57-3) were down-regulated in MTB-infected cells. We found that M0R050, O00442, Q9H8H0, O60812 and O43660 are interactive proteins which participate in a multitude of cellular RNA processing, suggesting that these five down-regulated proteins might repress the synthesis of some resistant proteins in MTB-infected cells to promote MTB survival in macrophages.


2007 ◽  
Vol 100 (2) ◽  
pp. 527-543 ◽  
Author(s):  
Xinmin Li ◽  
Hali Wang ◽  
Edward Touma ◽  
Emma Rousseau ◽  
Richard J. Quigg ◽  
...  

2021 ◽  
Vol 10 (14) ◽  
pp. 3060
Author(s):  
Mateusz Winiarczyk ◽  
Dagmara Winiarczyk ◽  
Katarzyna Michalak ◽  
Kai Kaarniranta ◽  
Łukasz Adaszek ◽  
...  

Macular edema and its further complications due to the leakage from the choroidal neovascularization in course of the age-related macular degeneration (AMD) is a leading cause of blindness among elderly individuals in developed countries. Changes in tear film proteomic composition have been reported to occur in various ophthalmic and systemic diseases. There is an evidence that the acute form of neovascular AMD may be reflected in the tear film composition. Tear film was collected with Schirmer strips from patients with neovascular AMD and sex- and age-matched control patients. Two-dimensional electrophoresis was performed followed by MALDI-TOF mass spectrometry for identification of differentially expressed proteins. Quantitative analysis of the differential electrophoretic spots was performed with Delta2D software. Altogether, 11 significantly differentially expressed proteins were identified; of those, 8 were downregulated, and 3 were upregulated in the tear film of neovascular AMD patients. The differentially expressed proteins identified in tear film were involved in signaling pathways associated with impaired protein clearance, persistent inflammation, and neovascularization. Tear film protein analysis is a novel way to screen AMD-related biomarkers.


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