scholarly journals A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

2020 ◽  
Vol 21 (11) ◽  
pp. 4187 ◽  
Author(s):  
Alexei Medvedev ◽  
Arthur Kopylov ◽  
Olga Buneeva ◽  
Leonid Kurbatov ◽  
Olga Tikhonova ◽  
...  
Keyword(s):  
Binding Sites ◽  
Binding Proteins ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Altered Expression ◽  
Peripheral Tissues ◽  
Brain Hemispheres ◽  
Wide Range ◽  
Brain Proteome ◽  
The Brain

Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes.

The effect of a neuroprotective dose of isatin or deprenyl to mice on the profile of brain isatin-binding proteins

2019 ◽  
Vol 65 (5) ◽  
pp. 407-417 ◽  
Author(s):  
O.A. Buneeva ◽  
I.G. Kapitsa ◽  
E.A. Ivanova ◽  
A.T. Kopylov ◽  
V.G. Zgoda ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Neuroprotective Effect ◽  
Proteomic Profiling ◽  
Pharmacological Activities ◽  
Dose Administration ◽  
Peripheral Tissues ◽  
Wide Range ◽  
Affinity Sorbent ◽  
The Brain

Isatin (indol-2,3-dione), an endogenous biofactor found in the brain, peripheral tissues and biological body fluids of humans and animals, exhibits a wide range of biological and pharmacological activities. They are realized via interaction with numerous isatin-binding proteins. Some of these proteins identified during proteomic profiling of the brain are involved in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl (selegiline), a pharmacological agent used for treatment of Parkinson's disease. In this study, we have investigated the effect of a single dose administration of isatin (100 mg/kg) and deprenyl (10 mg/kg) to mice on the profile of the brain isatin-binding proteins. Comparative proteomic analysis of brain isatin-binding proteins of mice treated with isatin or deprenyl resulted in identification of a representative group of proteins (n=200) sensitive to the administration of these substances. The change in the profile of isatin-binding proteins may be obviously attributed to accumulation of isatin and deprenyl in the brain and their interaction with target proteins; this prevents protein binding to the affinity sorbent. Thus identified brain isatin-binding proteins of the control animals obviously represent specific targets that interact directly with isatin (and also with deprenyl) in vivo. Isatin or deprenyl administered to animals interact with these proteins and thus inhibit their binding to the affinity sorbent (immobilized isatin analogue).

scholarly journals Hypoxia induced sex-difference in zebrafish brain proteome profile reveals the crucial role of H3K9me3 in recovery from acute hypoxia

2020 ◽  
Author(s):  
Tapatee Das ◽  
Avijeet Kamle ◽  
Arvind Kumar ◽  
Sumana Chakravarty
Keyword(s):  
Sex Difference ◽  
Acute Hypoxia ◽  
Differentially Expressed ◽  
Transcriptional Level ◽  
Differentially Expressed Proteins ◽  
Effective Prevention ◽  
Altered Expression ◽  
Zebrafish Brain ◽  
Neural Damage ◽  
Brain Proteome

ABSTRACTUnderstanding the molecular basis of sex differences in neural response to acute hypoxic insult has profound implications for the effective prevention and treatment of ischemic stroke. Global hypoxic-ischemic induced neural damage has been studied recently under the well-controlled, non-invasive, reproducible conditions using zebrafish model. Our earlier report on sex difference in global acute hypoxia induced neural damage and recovery in zebrafish prompted us for comprehensive study on the mechanisms underlying the recovery. An omics approach for studying quantitative changes in brain proteome upon hypoxia insult following recovery was undertaken using iTRAQ-based LC-MS/MS approach. The results shed light on altered expression of many regulatory proteins in zebrafish brain upon acute hypoxia following recovery. The sex difference in differentially expressed proteins along with the proteins expressed in uniform direction in both the sexes was studied. Core expression analysis by Ingenuity Pathway analysis (IPA) showed a distinct sex difference in the disease function heatmap. Most of the upstream regulators obtained through IPA were validated at the transcriptional level. Translational upregulation of H3K9me3 in male led us to elucidate the mechanism of recovery by confirming transcriptional targets through ChIP-qPCR. The upregulation of H3K9me3 level in male at 4 hr post-hypoxia appears to affect the early neurogenic markers nestin, klf4 and sox2, which might explain the late recovery in male, compared to female. Acute hypoxia-induced sex-specific comparison of brain proteome led us to reveal many differentially expressed proteins, which can be further studied for the development of novel targets for better therapeutic strategy.

scholarly journals Proteomics Analysis Reveals the Implications of Cytoskeleton and Mitochondria in the Response of the Rat Brain to Starvation

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 219 ◽  
Author(s):  
Beatriz Cuevas-Fernández ◽  
Carlos Fuentes-Almagro ◽  
Juan Peragón
Keyword(s):  
Mass Spectrometry ◽  
Rat Brain ◽  
Food Deprivation ◽  
Metabolic Response ◽  
Differentially Expressed ◽  
Nervous Impulse ◽  
Altered Expression ◽  
Peptide Mass ◽  
The Brain

Long-term starvation provokes a metabolic response in the brain to adapt to the lack of nutrient intake and to maintain the physiology of this organ. Here, we study the changes in the global proteomic profile of the rat brain after a seven-day period of food deprivation, to further our understanding of the biochemical and cellular mechanisms underlying the situations without food. We have used two-dimensional electrophoresis followed by mass spectrometry (2D-MS) in order to identify proteins differentially expressed during prolonged food deprivation. After the comparison of the protein profiles, 22 brain proteins were found with altered expression. Analysis by peptide mass fingerprinting and MS/MS (matrix-assisted laser desorption-ionization-time of flight mass spectrometer, MALDI-TOF/TOF) enabled the identification of 14 proteins differentially expressed that were divided into 3 categories: (1) energy catabolism and mitochondrial proteins; (2) chaperone proteins; and (3) cytoskeleton, exocytosis, and calcium. Changes in the expression of six proteins, identified by the 2D-MS proteomics procedure, were corroborated by a nanoliquid chromatography-mass spectrometry proteomics procedure (nLC-MS). Our results show that long-term starvation compromises essential functions of the brain related with energetic metabolism, synapsis, and the transmission of nervous impulse.

scholarly journals Proteomics reveals the preliminary physiological states of the spotted seal (Phoca largha) pups

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiashen Tian ◽  
Jing Du ◽  
Jiabo Han ◽  
Xiangbo Bao ◽  
Xinran Song ◽  
...  
Keyword(s):  
Whole Blood ◽  
Regulation Of Gene Expression ◽  
Protein Composition ◽  
Heat Shock Protein 90 ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Label Free ◽  
Spotted Seal ◽  
Phoca Largha ◽  
Wide Range

Abstract Spotted seal (Phoca largha) is a critically endangered pinniped in China and South Korea. The conventional method to protect and maintain the P. largha population is to keep them captive in artificially controlled environments. However, little is known about the physiological differences between wild and captive P. largha. To generate a preliminary protein expression profile for P. largha, whole blood from wild and captive pups were subjected to a label-free comparative proteomic analysis. According to the results, 972 proteins were identified and predicted to perform functions related to various metabolic, immune, and cellular processes. Among the identified proteins, the expression level of 51 were significantly different between wild and captive P. large pups. These differentially expressed proteins were enriched in a wide range of cellular functions, including cytoskeleton, phagocytosis, proteolysis, the regulation of gene expression, and carbohydrate metabolism. The abundances of proteins involved in phagocytosis and ubiquitin-mediated proteolysis were significantly higher in the whole blood of wild P. largha pups than in captive individuals. In addition, heat shock protein 90-beta, were determined as the key protein associated with the differences in the wild and captive P. largha pups due to the most interactions of it with various differentially expressed proteins. Moreover, wild P. largha pups could be more nutritionally stressed and have more powerful immune capacities than captive pups. This study provides the first data on the protein composition of P. largha and provides useful information on the physiological characteristics for research in this species.

scholarly journals Proteomic Study of Hypothalamus in Pigs Exposed to Heat Stress

2020 ◽  
Author(s):  
Tianyue Yu ◽  
Yan-Hong Yong ◽  
Jun-yu Li ◽  
Biao Fang ◽  
Can-ying Hu ◽  
...  
Keyword(s):  
Body Weight ◽  
Heat Stress ◽  
Regulatory Networks ◽  
Protein Profile ◽  
Absolute Quantification ◽  
The Body ◽  
Differentially Expressed ◽  
Farm Animals ◽  
Differentially Expressed Proteins ◽  
The Brain

Abstract Background : With evidence of warming climates, it is important to understand the effects of heat stress in farm animals in order to minimize production losses. Studying the changes in the brain proteome induced by heat stress may aid in understanding how heat stress affects brain function. The hypothalamus is a critical region in the brain that controls the pituitary gland, which is responsible for the secretion of several important hormones. In this study, we examined the hypothalamic protein profile of 10 pigs (15 ± 1 kg body weight), with five subjected to heat stress (35 ± 1 °C; relative humidity = 90%) and five acting as controls (28 ± 3°C; RH = 90%). Result: The isobaric tags for relative and absolute quantification (iTRAQ) analysis of the hypothalamus identified 1710 peptides corresponding to 360 proteins, including 295 differentially expressed proteins (DEPs), 148 of which were up-regulated and 147 down-regulated, in heat-stressed animals. The Ingenuity Pathway Analysis (IPA) software predicted 30 canonical pathways, four functional groups, and four regulatory networks of interest. The DEPs were mainly concentrated in the cytoskeleton of the pig hypothalamus during heat stress. Conclusions: In this study, heat stress significantly increased the body temperature and reduced daily gain of body weight in pigs. Furthermore, we identified 295 differentially expressed proteins, 147 of which were down-regulated and 148 up-regulated in hypothalamus of heat stressed pigs. The IPA showed that the DEPs identified in the study are involved in cell death and survival, cellular assembly and organization, and cellular function and maintenance, in relation to neurological disease, metabolic disease, immunological disease, inflammatory disease, and inflammatory response. We hypothesize that a malfunction of the hypothalamus may destroy the host physical and immune function, resulting in decreased growth performance and immunosuppression in heat stressed pigs.

iTRAQ-Based Quantitative Proteomic Analysis of Pseudostellaria heterophylla from Geo-Authentic Habitat and Cultivated Bases

2019 ◽  
Vol 16 (3) ◽  
pp. 231-245
Author(s):  
Yujiao Hua ◽  
Chengcheng Wang ◽  
Shengnan Wang ◽  
Zixiu Liu ◽  
Xunhong Liu ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Large Subunit ◽  
Absolute Quantification ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Realtime Pcr ◽  
Pseudostellaria Heterophylla ◽  
Response To Stress ◽  
Isobaric Tags ◽  
Shock Proteins

Background: Pseudostellaria heterophylla is an important tonic traditional Chinese medicine. However, the molecular changes in the herb from geo-authentic habitat and cultivated bases remain to be explored. Objective: The purpose of this research was to study differences in P. heterophylla from geo-authentic habitat and cultivated bases. Methods: High-throughput technologies of transcriptomic and proteomic were used to identify proteins. Isobaric Tags for Relative and Absolute Quantification (iTRAQ) MS/MS has been utilized to evaluate changes in P. heterophylla from geo-authentic habitat and cultivated bases. Results: In this study, a total of 3775 proteins were detected, and 140 differentially expressed proteins were found in P. heterophylla from geo-authentic habitat and cultivated bases. 44 significantly differential expressed proteins were identified based on functional analysis classified into nine categories. Five differentially expressed proteins were confirmed at the gene expression level by Quantitative realtime PCR. Catabolic metabolism, carbohydrate metabolism, and response to stress of oxidoreductases and transferases in P. heterophylla from geo-authentic habitat were stronger than in those from cultivated bases, but protein folding and response to stress of heat shock proteins, isomerases, rubisco large subunit-binding proteins, chaperone proteins, and luminal-binding proteins in herbs from cultivated bases were more active. ADG1 and TKTA could be the critical proteins to regulate sucrose; MFP2 and CYS may be the crucial proteins that control the metabolism of fatty acids and amino acids. Conclusion: These results will provide the basic information for exploring the differences in secondary metabolites in P. heterophylla from geo-authentic habitat and cultivated bases and the protein mechanism of its quality formation.

scholarly journals Discovery and Verification of Gelsolin as a Potential Biomarker of Colorectal Adenocarcinoma in a Chinese Population: Examining Differential Protein Expression using an Itraq Labelling-Based Proteomics Approach

2012 ◽  
Vol 26 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Nai-Jun Fan ◽  
Chun-Fang Gao ◽  
Chang-Song Wang ◽  
Jing-Jing Lv ◽  
Guang Zhao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Protein Identification ◽  
Colorectal Adenocarcinoma ◽  
Biomarker Discovery ◽  
Differentially Expressed ◽  
Screening Tests ◽  
Differentially Expressed Proteins ◽  
Potential Biomarker ◽  
Wide Range

Despite the wide range of available colorectal cancer (CRC) screening tests, less than 50% of cases are detected at early stages. However, the identification of differentially expressed proteins or novel protein biomarkers in CRC may have some utility and, ultimately, improve patient care and survival. Proteomics combined with mass spectroscopy and liquid chromatography are emerging as powerful tools that have led to the discovery of potential markers in cancer biomarker discovery in several types of cancers. This article describes a novel technology that uses isotopic reagents to tag selected proteins that show a consistent pattern of differential expression in CRC.OBJECTIVE: To identify and validate potential biomarkers of colorectal adenocarcinoma using a proteomic approach.METHODS: Multidimensional liquid chromatography/mass spectrometry was used to analyze biological samples labelled with isobaric mass tags for relative and absolute quantitation to identify differentially expressed proteins in human colorectal adenocarcinoma and paired normal mucosa for the discovery of cancerous biomarkers. Cancerous and noncancerous samples were compared using online and offline separation. Protein identification was performed using mass spectrometry. The downregulation of gelsolin protein in colorectal adenocarcinoma samples was confirmed by Western blot analysis and validated using immunohistochemistry.RESULTS: A total of 802 nonredundant proteins were identified in colorectal adenocarcinoma samples, 82 of which fell outside the expression range of 0.8 to 1.2, and were considered to be potential cancer-specific proteins. Immunohistochemistry revealed a complete absence of gelsolin expression in 86.89% of samples and a reduction of expression in 13.11% of samples, yielding a sensitivity of 86.89% and a specificity of 100% for distinguishing colorectal adenocarcinoma from normal tissue.CONCLUSIONS: These findings suggest that decreased expression of gelsolin is a potential biomarker of colorectal adenocarcinoma.

scholarly journals Proteomic Study of Hypothalamus in Pigs Exposed to Heat Stress

2020 ◽  
Author(s):  
Tianyue Yu ◽  
Yan-Hong Yong ◽  
Jun-yu Li ◽  
Biao Fang ◽  
Can-ying Hu ◽  
...  
Keyword(s):  
Body Weight ◽  
Heat Stress ◽  
Regulatory Networks ◽  
Protein Profile ◽  
Absolute Quantification ◽  
The Body ◽  
Differentially Expressed ◽  
Farm Animals ◽  
Differentially Expressed Proteins ◽  
The Brain

Abstract Background : With evidence of warming climates, it is important to understand the effects of heat stress in farm animals in order to minimize production losses. Studying the changes in the brain proteome induced by heat stress may aid in understanding how heat stress affects brain function. The hypothalamus is a critical region in the brain that controls the pituitary gland, which is responsible for the secretion of several important hormones. In this study, we examined the hypothalamic protein profile of 10 pigs (15 ± 1 kg body weight), with five subjected to heat stress (35 ± 1 °C; relative humidity = 90%) and five acting as controls (28 ± 3°C; RH = 90%). Result: The isobaric tags for relative and absolute quantification (iTRAQ) analysis of the hypothalamus identified 1710 peptides corresponding to 360 proteins, including 295 differentially expressed proteins (DEPs), 148 of which were up-regulated and 147 down-regulated, in heat-stressed animals. The Ingenuity Pathway Analysis (IPA) software predicted 30 canonical pathways, four functional groups, and four regulatory networks of interest. The DEPs were mainly concentrated in the cytoskeleton of the pig hypothalamus during heat stress. Conclusions: In this study, heat stress significantly increased the body temperature and reduced daily gain of body weight in pigs. Furthermore, we identified 295 differentially expressed proteins, 147 of which were down-regulated and 148 up-regulated in hypothalamus of heat stressed pigs. The IPA showed that the DEPs identified in the study are involved in cell death and survival, cellular assembly and organization, and cellular function and maintenance, in relation to neurological disease, metabolic disease, immunological disease, inflammatory disease, and inflammatory response. We hypothesize that a malfunction of the hypothalamus may destroy the host physical and immune function, resulting in decreased growth performance and immunosuppression in heat stressed pigs.

scholarly journals The effect of deprenyl and isatin administration to mice on the proteomic profile of liver isatin-binding proteins

2018 ◽  
Vol 64 (4) ◽  
pp. 354-359 ◽  
Author(s):  
O.A. Buneeva ◽  
A.T. Kopylov ◽  
V.G. Zgoda ◽  
A.E. Medvedev
Keyword(s):  
Binding Proteins ◽  
Low Dose ◽  
Wide Spectrum ◽  
Neuroprotective Effect ◽  
Proteomic Profiling ◽  
Peripheral Tissues ◽  
Affinity Ligand ◽  
Affinity Sorbent ◽  
The Brain

Isatin (indol-2,3-dione) is an endogenous indole found in the brain, peripheral tissues and biological body fluids of humans and animals. Its wide spectrum of biological activity is realized via interaction with numerous isatin-binding proteins; these include proteins playing an important role in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl, a pharmacological agent used for treatment of Parkinson's disease. In this study, the effects of the course of deprenyl (1 mg/kg) and isatin (20 mg/kg) administration for 21 days on the profile of the isatin-binding proteins of the liver of mice have been investigated. Proteomic profiling of liver isatin-binding proteins of control mice by means of 5-aminocaproylisatin as an affinity ligand resulted in identification of 105 proteins. Treatment of animals with a low dose of isatin slightly decreased (up to 91), while injections of deprenyl slightly increased (up to 120) the total number of isatin-binding proteins. 75 proteins were common for all three groups; they represented from 62.5% (in deprenyl treated mice) and 71% (in control mice), to 82% (isatin treated mice) of the total number of identified liver isatin-binding proteins. Proteomic analysis of the isatin-binding proteins of mice treated with isatin (20 mg/kg) or deprenyl (1 mg/kg) for 21 days revealed a representative group of proteins (n=30) that were sensitive to the administration of these substances. Taking into account the previously obtained results, it is reasonable to suggest that the change in the profile of isatin-binding proteins may be attributed to accumulation of isatin and deprenyl in the liver and interaction with target proteins prevents their subsequent binding to the affinity sorbent. In this context, the identified isatin-binding liver proteins of control animals that do not bind to the affinity sorbent (immobilized isatin analogue) after treatment of animals with either deprenyl or isatin appear to be specific targets directly interacting with isatin in vivo.

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