ABSTRACT
The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity. However, the transformation of current genetic variant-obesity associations into biological knowledge has been proven challenging. Genomics and proteomics are complementary fields, as proteomics extends functional analyses. Integrating genomic and proteomic data can help to bridge a gap in knowledge regarding genetic variant-obesity associations and to identify new drug targets for the treatment of obesity. We provide an overview of the published papers on the integrated analysis of proteomic and genomic data in obesity and summarize four mainstream strategies: overlap, colocalization, Mendelian randomization, and proteome-wide association studies. The integrated analyses identified many obesity-associated proteins, such as leptin, follistatin, and adenylate cyclase 3. Despite great progress, integrative studies focusing on obesity are still limited. There is an increased demand for large prospective cohort studies to identify and validate findings, and further apply these findings to the prevention, intervention, and treatment of obesity. In addition, we also discuss several other potential integration methods.
Subject(s)
Humans , Proteome/metabolism , Proteomics , Prospective Studies , Obesity/genetics , Genomics , Genome-Wide Association StudyABSTRACT
The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.
Subject(s)
Animals , Mice , Chromatography, Liquid , Drugs, Chinese Herbal/pharmacology , Hippocampus/metabolism , Proteome/metabolism , Proteomics , Tandem Mass SpectrometryABSTRACT
Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.
Subject(s)
Animals , Male , Mice , Acetylation , Aging , Liver , Lysine/metabolism , Mice, Inbred C57BL , Proteome/metabolismABSTRACT
In the past decade, relative proteomic quantification using isobaric labeling technology has developed into a key tool for comparing the expression of proteins in biological samples. Although its multiplexing capacity and flexibility make this a valuable technology for addressing various biological questions, its quantitative accuracy and precision still pose significant challenges to the reliability of its quantification results. Here, we give a detailed overview of the different kinds of isobaric mass tags and the advantages and disadvantages of the isobaric labeling method. We also discuss which precautions should be taken at each step of the isobaric labeling workflow, to obtain reliable quantification results in large-scale quantitative proteomics experiments. In the last section, we discuss the broad applications of the isobaric labeling technology in biological and clinical studies, with an emphasis on thermal proteome profiling and proteogenomics.
Subject(s)
Proteome/metabolism , Proteomics/methods , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.
Subject(s)
Acetylation , Lysine/metabolism , Oryza/metabolism , Plant Proteins/metabolism , Protein Interaction Maps , Protein Processing, Post-Translational , Proteome/metabolism , Ubiquitin/metabolism , UbiquitinationABSTRACT
La glándula mamaria y la leche materna son el resultado de millones de años de una evolución que llevó a una composición óptima para el crecimiento y desarrollo de recién nacidos y lactantes; la leche materna favorece el crecimiento, la adaptación y la supervivencia de su organismo y de sus órganos inmaduros. Análisis recientes han demostrado en ella la presencia de 1606 proteínas que en su mayoría son sintetizadas en los acinos de la glándula mamaria aunque otras proteínas y péptidos provienen de órganos como el sistema linfático y el aparato digestivo. La composición de la leche materna incluye enzimas que modifican sus proteínas y originan péptidos antimicrobianos, antihipertensivos y estimuladores del metabolismo. Esta actividad proteolítica actúa en sitios específicos de las cadenas peptídicas de la proteína de la leche. La activación extemporánea de estos enzimas en los acinos es regulada por péptidos inhibidores y activadores que previenen procesos inflamatorios. Algunos enzimas de la leche actúan en el tubo digestivo de recién nacidos y lactantes y complemen tan la menor concentración y actividad de sus propios enzimas digestivos. Así, la enteroquinasa de la leche estimula la liberación de enzimas pancreáticos (mediada por el estímulo de la colecistoquinina-pancreozimina); la lipasa activada por las sales biliares complementa la baja producción de lipasa pancreática. Estas actividades probablemente facilitan la nutrición de los prematuros, cuyo tubo di gestivo es más permeable a las proteínas parcialmente hidrolizadas y cuyas actividades enzimáticas y factores defensivos locales no han alcanzado su plena madurez. Esto también puede estimular en ellos la tolerancia inmunológica. En este artículo se presentan los aspectos fisiológicos relevantes de la leche materna, y los avances en el conocimiento de su composición, para el cabal conocimiento del pediatra de esta importante materia.
The mammary gland and maternal milk are the product of millions of years of evolution that resul ted in an optimal composition that sustains the growth and development of newborns and infants. Maternal milk supports the growth, adaptation and survival of this immature organism. Recent studies have detected 1606 different proteins in human milk, most of them synthesized in the acini of the glandular tissue while others originate from distant organs such as the lymphoid tissue and the digestive tract. Maternal milk enzymes modify its proteins and liberate peptides with antimicrobial, antihypertensive or stimulatory activities. This proteolytic activity occurs at specific sites in peptide chains. To prevent the extemporaneous activation of these proteolytic enzymes, that would result in inflammatory processes, maternal milk also contains inhibitory peptides that together with the stimulatory peptides conform a complex regulatory system. Some enzymes in maternal milk main tain their activity in the gastrointestinal tract of infants and compensate for the decreased activity of digestive tract enzymes in newborns. Thus, the milk enterokynase stimulates the release of pancreatic proteases as it induces the liberation of cholecystokynin/pancreozymin. The bile salt-activated lipase of human milk is activated in the duodenum by the infants' bile salts and partially compensates for the low levels of pancreatic lipase in newborns. These milk enzymes probably contribute to the nutrition of premature infants as they increase the availability of amino acids and peptides in their upper gastrointestinal tract; furthermore, as their intestinal epithelium is more permeable to peptides and partially digested protein this may help induce immune tolerance. The most relevant issues in the physiology and composition of the maternal milk are presented in this review.
Subject(s)
Humans , Proteome/metabolism , Milk, Human/metabolism , Milk Proteins/metabolism , Mammary Glands, Human/physiology , Biological EvolutionABSTRACT
Abstract: Introduction: Relapse occurs in approximately 20% of Mexican patients with childhood acute lymphoblastic leukemia (ALL). In this group, chemoresistance may be one of the biggest challenges. An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies. Methods: The B-lineage pediatric ALL cell line CCRF-SB was gradually exposed to the chemotherapeutic vincristine until proliferation was observed at 6 nM, control cells were cultured in the absence of vincristine. The proteome from each group was analyzed by nanoHPLC coupled to an ESI-ion trap mass spectrometer. The identified proteins were grouped into over-represented functional categories with the PANTHER classification system. Results: We found 135 proteins exclusively expressed in the presence of vincristine. The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation. Conclusions: Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets.
Resumen: Introducción: Aproximadamente el 20% de los pacientes mexicanos con leucemia linfoblástica aguda (LLA) infantil presentan recaídas. En este grupo, la quimiorresistencia es uno de los principales desafíos. Los estudios proteómicos pueden dar un panorama general de procesos celulares complejos como la tolerancia a fármacos. Métodos: La línea celular de LLA de linaje B, CCRF-SB, fue expuesta de manera gradual al fármaco quimioterapéutico vincristina hasta observar proliferación celular en presencia de 6 nM, como control se cultivaron células en ausencia del fármaco. Se analizó el proteoma de cada grupo mediante nanoHPLC acoplado a un espectrómetro de masas de tipo trampa de iones. Las proteínas identificadas se agruparon en categorías funcionales sobre-representadas con el sistema de clasificación PANTHER. Resultados: Encontramos 135 proteínas expresadas exclusivamente en presencia de vincristina. Las categorías funcionales más representadas fueron la señalización asociada a los receptores tipo Toll, señalización dependiente de Ras, activación de células B y T, mapa de señalización CCKR, señalización mediada por citoquinas y la fosforilación oxidativa. Conclusiones: Nuestro estudio indica que la transducción de señales y la producción de ATP mitocondrial son procesos esenciales durante la adaptación de células leucémicas a vincristina por lo que estos procesos representan potenciales blancos terapéuticos.
Subject(s)
Child , Humans , Vincristine/pharmacology , Proteomics/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Signal Transduction/drug effects , Proteins/metabolism , Gene Expression Regulation, Leukemic , Adenosine Triphosphate/metabolism , Chromatography, High Pressure Liquid , Drug Resistance, Neoplasm , Proteome/metabolism , Spectrometry, Mass, Electrospray Ionization , Cell Line, Tumor , Cell Proliferation/drug effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Mitochondria/metabolismABSTRACT
OBJECTIVES@#To establish the imaging mass spectrometry for analysis of differentially expressed proteins distribution in the rat brains with diffuse axonal injury (DAI) based on matrix assisted laser desorption/ionization-time of flight imaging mass spectrometry (MALDI-TOF-IMS).@*METHODS@#MALDI-TOF-IMS scanning were conducted on the brains of DAI group and control group in the m/z range of 1 000 to 20 000 using AutoflexⅢ MALDI-TOF spectrometer. ClinProTool 2.2 software was used for statistical analysis on the data of two groups, and then the differentially expressed proteins were picked out to conduct imaging. The distribution of the proteins with different m/z in the rat brains was observed.@*RESULTS@#Five proteins with different m/z, including 4 963, 5 634, 6 253, 6 714 and 7 532, differentially expressed in the rat brains with DAI.@*CONCLUSIONS@#MALDI-TOF-IMS can be used for studying the differentially expressed proteins in rat brains with DAI and the analysis method is established for exploring the distribution of differentially expressed proteins in the rat brains with DAI using imaging mass spectrometry.
Subject(s)
Animals , Rats , Brain/pathology , Diffuse Axonal Injury/pathology , Proteins/metabolism , Proteome/metabolism , Proteomics , Software , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Preeclampsia is one of the most important and complexed disorders for women's health. Searching for novel proteins as biomarkers to reveal pathogenesis, proteomic approaches using 2DE has become a valuable tool to understanding of preeclampsia. To analyze the proteomic profiling of preclamptic placenta compared to that of normal pregnancy for better understanding of pathogenesis in preeclampsia, placentas from each group were handled by use of proteomics approach using 2DE combined with MALDI-TOF-MS. The 20 spots of showing differences were analysed and identified. Among differentially expressed protein spots Hsp 27 and Hsp 70 were selected for validation using Western blot analysis. In preeclamptic placenta 9 differentially expressed proteins were down-regulated with Hsp 70, serum albumin crystal structure chain A, lamin B2, cytokeratin 18, actin cytoplasmic, alpha fibrinogen precursor, septin 2, dihydrolipoamide branched chain transacylase E2 and firbrinogen beta chain. The 11 up-regulated proteins were fibrinogen gamma, cardiac muscle alpha actin proprotein, cytokeratin 8, calumenin, fibrinogen fragment D, F-actin capping protein alpha-1 subunit, Hsp 27, Hsp 40, annexin A4, enoyl-CoA delta isomerase and programmed cell death protein 6. The western blot analysis for validation also showed significant up-regulation of Hsp 27 and down-regulation of Hsp 70 in the placental tissues with preeclmaptic pregnancies. This proteomic profiling of placenta using 2DE in preeclampsia successfully identifies various proteins involved in apoptosis, mitochondrial dysfunction, as well as three Hsps with altered expression, which might play a important role for the understanding of pathogenesis in preeclampsia.
Subject(s)
Adult , Female , Humans , Placenta/metabolism , Pre-Eclampsia/metabolism , Pregnancy/metabolism , Proteome/metabolism , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The chronic diabetes mellitus (DM) is a major risk factor for cardiovascular disease. The incidence of cardiovascular disease might be a foremost cause of morbidity and mortality in patients afflicted with DM. In fact, DM is associated with multi-factorial cardiovascular signalling alterations via significant modulation of expression pattern, activation or release of PI3K, PKB, eNOS, EDRF, NADPH oxidase, EDHF, CGRP, adenosine, iNOS, ROCK, PKC-β2, CaMKII, microRNA (miR)-126 and miR-130a, which could result in inadequate maintenance of cardiovascular physiology and subsequent development of cardiovascular pathology. This review highlights the possible adverse implications of fundamental cardiovascular signalling alteration in DM-associated cardiovascular disease pathology.
Subject(s)
Animals , Coronary Artery Disease/metabolism , Diabetes Complications/metabolism , Diabetic Angiopathies/metabolism , Humans , Models, Cardiovascular , Proteome/metabolism , Signal Transduction , /metabolismSubject(s)
Bacterial Proteins/genetics , Ethanol/pharmacology , Gene Expression Regulation, Bacterial , Genes, Regulator , Proteome/genetics , Synechocystis/drug effects , Adaptation, Physiological , Amino Acid Motifs , Biofuels , Bacterial Proteins/metabolism , Ethanol/metabolism , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Molecular Sequence Annotation , Molecular Sequence Data , Promoter Regions, Genetic , Protein Binding , Photosynthesis/drug effects , Proteome/metabolism , Sodium-Bicarbonate Symporters/genetics , Sodium-Bicarbonate Symporters/metabolism , Synechocystis/genetics , Synechocystis/growth & development , Synechocystis/metabolism , Transcription, GeneticABSTRACT
Objetivos: Determinar la probabilidad de riesgo suicida y/o enfermedad mental y factores asociados en estudiantes de secundaria de tres colegios bogotanos. Métodos: Estudio de corte transversal con 309 adolescentes. Resultados: El promedio de edad fue de 13,83 ± 0,9 años, predominó el género femenino (58,6%) y el estrato socioeconómico 3 (68,3%). La probabilidad de riesgo para comportamiento suicida y/o síntomas mentales fue de 47,6%; 26,5% tuvo alguna manifestación suicida; 14,23% tuvo ideación suicida en los últimos tres meses; 3,55% tuvo intentos suicidas alguna vez en la vida, y 8,73% tuvo ideación suicida e intentos suicidas en los últimos tres meses. El riesgo de comportamiento suicida y/o enfermedad mental fue explicado conjuntamente por la depresión (OR = 27,9, IC95% = 3,5-223,1), la baja autoestima (OR = 11,8, IC95% = 2,5-56,5), la disfunción familiar severa (OR = 3,4, IC95% = 1,2-9,7), el sexo femenino (OR = 2,1, IC95% = 1,2-3,8) y la edad mayor o igual a 15 años (OR = 1,9, IC95% = 0,9-3,9). El maltrato psicológico seguido del abuso físico se asociaron con manifestación suicida y/o enfermedad mental, y la buena relación familiar, con menor probabilidad. Conclusión: La depresión, la baja autoestima, la disfuncionalidad familiar, el género femenino, la edad > 15 y la violencia intrafamiliar son factores asociados al riesgo suicida y/o enfermedad mental en adolescentes, y las buenas relaciones familiares se asocian con menor riesgo.
Objective: To establish the probability for suicide risk and/or mental disorders, together with related factors among high school students in 3 schools in Bogota. Methods: Cross sectional study of 309 adolescents. Results: The average age was 13.83 ± 0.9, female dominance (58.6%) and a 3rd socioeconomic stratum (68.3%). The suicidal risk behavioral probability and/or mental symptoms was 47.6%, 26.5% exhibited some suicide manifestations, 14.23% had experienced suicidal ideas in the last 3 months, 3.55% had had suicide attempts at least once in life, and 8.73% had suicidal ideas in the last 3 months with suicide attempts. The risk of suicidal behavior and /or mental disorders was explained jointly by depression (OR=27.9, 95% CI: 3.5-223. 1), low self-esteem (OR=11.8, 95% CI: 2.5-56.5), severe family dysfunction (OR=3.4, 95%CI 1.2-9.7), being female (OR=2.1, 95% CI: 1.2-3.8) and being 15 or older (OR=1.9, 95% CI: 0.967-3.9). Psychological abuse followed by physical mistreatment was associated with suicidal behavior and /or mental illness while good family relationships were associated to lower probability. Conclusion: Depression, low self-esteem, severe family dysfunction, female gender, older age (> 15) and domestic violence are risk factors associated with suicide and/or mental disorders in adolescents; good family relationships are associated with lower risk.
Subject(s)
Female , Humans , Endopeptidases/chemistry , Milk Proteins/chemistry , Milk, Human/chemistry , Peptides/analysis , Proteome/chemistry , Amino Acid Sequence , Endopeptidases/metabolism , Molecular Sequence Data , Milk Proteins/metabolism , Peptide Mapping , Proteolysis , Peptides/chemistry , Peptides/metabolism , Proteome/metabolism , Substrate SpecificityABSTRACT
Crystallins are a diverse group of proteins that constitute nearly 90% of the total soluble proteins of the vertebrate eye lens and these tightly packed crystallins are responsible for transparency of the lens. These proteins have been studied in different model and non-model species for understanding the modifications they undergo with ageing that lead to cataract, a disease of protein aggregation. In the present investigation, we studied the lens crystallin profile of the tropical freshwater catfish Rita rita. Profiles of lens crystallins were analyzed and crystallin proteome maps of Rita rita were generated for the first time. A-crystallins, member of the -crystallin family, which are molecular chaperons and play crucial role in maintaining lens transparency were identified by 1-and 2-D immunoblot analysis with anti-A-crystallin antibody. Two protein bands of 19-20 kDa were identified as A-crystallins on 1-D immunoblots and these bands separated into 10 discrete spots on 2-D immunoblot. However, anti-B-crystallin and antiphospho-B-crystallin antibodies were not able to detect any immunoreactive bands on 1- and 2-D immunoblots, indicating B-crystallin was either absent or present in extremely low concentration in Rita rita lens. Thus, Rita rita -crystallins are more like that of the catfish Clarias batrachus and the mammal kangaroo in its A- and B-crystallin content (contain low amount from 5-9% of aB-crystallin) and unlike the dogfish, zebrafish, human, bovine and mouse -crystallins (contain higher amount of B-crystallin from 25% in mouse and bovine to 85% in dogfish). Results of the present study can be the baseline information for stimulating further investigation on Rita rita lens crystallins for comparative lens proteomics. Comparing and contrasting the -crystallins of the dogfish and Rita rita may provide valuable information on the functional attributes of A- and B-isoforms, as they are at the two extremes in terms of A-and B-crystallin content.
Subject(s)
Animals , Cataract/pathology , Catfishes/metabolism , Cattle , Crystallins/isolation & purification , Crystallins/metabolism , Electrophoresis, Gel, Two-Dimensional/methods , Humans , Macropodidae/metabolism , Mice , Proteome/metabolism , alpha-Crystallin A Chain/isolation & purification , alpha-Crystallin A Chain/metabolism , alpha-Crystallin B Chain/isolation & purification , alpha-Crystallin B Chain/metabolism , alpha-Crystallins/isolation & purification , alpha-Crystallins/metabolismABSTRACT
Hepatitis B virus initiates a complicated cascade process leading to chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. In inflammatory situations, myeloperoxidase is released in plasma and binds to apolipoprotein A-1 in high-density lipoproteins. This study aims to evaluate the level of plasma myeloperoxidase as well as the pattern of plasma proteins in patients with chronic hepatitis B. Included in this study were 30 male subjects: 19 chronic hepatitis B patients, 6 HBV-related cirrhotic patients, and 5 healthy controls. Plasma myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proteomic analysis of plasma proteins was performed by two-dimensional gel electrophoresis [2-DE] and mass spectrometry. One way ANOVAwas used for data analysis. Mean plasma myeloperoxidase levels were higher in patients with liver cirrhosis [65.5 +/- 12.5; P=0.007] and chronic hepatitis B [53.7 +/- 10.6; P=0.18] when compared with healthy subjects [45 +/- 7.6]. Moreover, a positive correlation was found between plasma myeloperoxidase levels and hepatic fibrosis stage [r=0.53, P=0.002; r=0.63, P=0.000]. Proteomic analysis showed an altered plasma protein pattern in progressive hepatitis B and down-regulation of the major apolipoprotein A-1 along with the appearance of a variety of spots noted to be apolipoprotein A-1isoforms with different molecular masses. In this study, progressive liver injury due to HBV infection correlated with higher plasma myeloperoxidase and an altered plasma apolipoprotein A-1 pattern
Subject(s)
Humans , Adult , Middle Aged , Male , Apolipoprotein A-I/blood , Hepatitis B, Chronic/enzymology , Liver Cirrhosis/enzymology , Liver Cirrhosis/virology , Liver Cirrhosis/metabolism , Hepatitis B virus , Hepatitis B, Chronic/metabolism , Analysis of Variance , Down-Regulation , Proteome/metabolismABSTRACT
Successful hematopoietic stem cell transplantation (HSCT) involves the restoration of hematopoietic function after engraftment, arising from the differentiation and proliferation of hematopoietic stem cells. Several factors could influence the course of allogeneic-HSCT (allo-HSCT). Therefore, knowledge of serum proteome changes during the allo-HSCT period might increase the efficacy of diagnosis and disease prevention efforts. This study conducted proteomic analyses to find proteins that were significantly altered in response to allo-HSCT. Sera from five representative patients who underwent allo-HSCT were analyzed by 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry, and were measured on a weekly basis before and after allo-HSCT in additional 78 patients. Fourteen protein spots showing changes in expression were further examined, and most proteins were identified as acute phase proteins (APPs). Studies of 78 additional patients confirmed that C-reactive protein (CRP) and haptoglobin undergo expression changes during allo-HSCT and thus may have the potential to serve as representative markers of clinical events after allo-HSCT. Maximal CRP level affected the development of major transplant-related complications (MTCs) and other problems such as fever of unknown origin. Particularly, an increase in CRP level 21 days after allo-HSCT was found to be an independent risk factor for MTC. Maximal haptoglobin and haptoglobin level 14 days after allo-HSCT were predictive of relapses in underlying hematologic disease. Our results indicated that CRP and haptoglobin were significantly expressed during allo-HSCT, and suggest that their level can be monitored after allo-HSCT to assess the risks of early transplant-related complications and relapse.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Biomarkers , C-Reactive Protein/metabolism , Haptoglobins/metabolism , Hematopoietic Stem Cell Transplantation/adverse effects , Proteome/metabolism , Proteomics , Transplantation Conditioning , Transplantation, HomologousABSTRACT
Electroconvulsive therapy (ECT) is one of the most effective treatments used in psychiatry to date. The mechanisms of ECT action, however, are the least understood and still unclear. As a tool to elucidate the mechanisms of action of ECT, we employed proteomic analysis based on the identification of differentially expressed proteins after exposure to repeated ECT in rat brains. The expression of proteins was visualized by silver stain after two-dimensional gel electrophoresis. Of 24 differentially expressed protein spots (p<0.05 by Student t-test), six different proteins from 7 spots were identified by matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF)/mass spectrometry. Among the identified proteins, there were five dominantly expressed proteins in the ECT-treated rat brain tissues (p<0.05); S100 protein beta chain, 14-3-3 protein zeta/delta, similar to ubiquitin-like 1 (sentrin) activating enzyme subunit 1, suppressor of G2 allele of SKP1 homolog, and phosphatidylinositol transfer protein alpha. The expression of only one protein, ACY1 protein, was repressed (p<0.05). These findings likely serve for a better understanding of mechanisms involved in the therapeutic effects of ECT.