scholarly journals Effects of the glucocorticoid drug prednisone on urinary proteome and candidate biomarkers

2017 ◽  
Author(s):  
Jianqiang Wu ◽  
Xundou Li ◽  
Manxia An ◽  
Youhe Gao
Keyword(s):  
Drug Efficacy ◽  
Clinical Proteomics ◽  
Label Free ◽  
Urinary Proteins ◽  
Rat Urine ◽  
Urine Proteome ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Prednisone Treatment ◽  
Human Orthologs

AbstractUrine is a good source of biomarkers for clinical proteomics studies. However, one challenge in the use of urine biomarkers is that outside factors can affect the urine proteome. Prednisone is a commonly prescribed glucocorticoid used to treat various diseases in the clinic. To evaluate the possible impact of glucocorticoid drugs on the urine proteome, specifically disease biomarkers, this study investigated the effects of prednisone on the rat urine proteome. Urine samples were collected from control rats and prednisone-treated rats after drug administration. The urinary proteome was analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and proteins were identified using label-free proteome quantification. Differentially expressed proteins and their human orthologs were analyzed with bioinformatics methods. A total of 523 urinary proteins were identified in rat urine. Using label-free quantification, 27 urinary proteins showed expression changes after prednisone treatment. A total of 16 proteins and/or their human orthologs have been previously annotated as disease biomarkers. After functional analysis, we found that the pharmacological effects of prednisone were reflected in the urine proteome. Thus, urinary proteomics has the potential to be a powerful drug efficacy monitoring tool in the clinic. Meanwhile, alteration of the urine proteome due to prednisone treatment should be considered in future disease biomarker studies.

scholarly journals Regional differences of the urinary proteomes in healthy Chinese individuals

2017 ◽  
Author(s):  
Jianqiang Wu ◽  
Weiwei Qin ◽  
Li Pan ◽  
Fanshuang Zhang ◽  
Xiaorong Wang ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Regional Differences ◽  
Large Scale ◽  
Differentially Expressed ◽  
Clinical Proteomics ◽  
Label Free ◽  
Sample Collection ◽  
Urine Proteome ◽  
Disease Biomarkers ◽  
Urine Biomarker

AbstractUrine is a promising biomarker source for clinical proteomics studies. Although regional physiological differences are common in multi-center clinical studies, the presence of significant differences in the urinary proteomes of individuals from different regions remains unknown. In this study, morning urine samples were collected from healthy urban residents in three regions of China and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among the three regions. We identified 1,898 proteins from Urimem samples using label-free proteome quantification, of which 62 urine proteins were differentially expressed among the three regions. Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. Of the 62 differentially expressed proteins, 10 have been reported to be disease biomarkers in previous clinical studies. Urimem facilitates urinary protein storage for large-scale urine sample collection, and thus accelerates biobank development and urine biomarker studies employing proteomics approaches. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.

scholarly journals Effects of anesthetics pentobarbital sodium and chloral hydrate on urine proteome

2015 ◽  
Author(s):  
Mindi Zhao ◽  
Youhe Gao
Keyword(s):  
Nervous System ◽  
Chloral Hydrate ◽  
Biomarker Discovery ◽  
Animal Experiments ◽  
Label Free ◽  
Urinary Proteins ◽  
Healthy Human ◽  
Rat Urine ◽  
Pentobarbital Sodium ◽  
Urine Proteome

Background. Urine can be a better source than blood for biomarker discovery since it accumulates many changes. The urine proteome is susceptible to many factors including anesthesia. Pentobarbital sodium and chloral hydrate are commonly used anesthetics in animal experiments. Methods. This study demonstrated effects of these two anesthetics on the rat urine proteome using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results. With anesthesia, the urinary protein-to-creatinine ratio of all rats increased two fold. The relative abundance of 22 and 23 urinary proteins were changed with pentobarbital sodium or chloral hydrate anesthesia, respectively, as determined by label-free quantification. Among these changed proteins, fifteen had been considered as candidate biomarkers such as uromodulin, sixteen had been considered stable in healthy human urine, which are more likely to be considered as potential biomarkers when changed, such as transferrin. Discussion. The pattern of changed urinary proteins provides clues to the discovery of urinary proteins regulatory mechanisms. When determining candidate biomarker, anesthetic-related effects can be excluded in future biomarker discovery studies. Since anesthetics take effects via nervous system, this study is the first to provide clues that protein handling function of kidney may possibly be regulated by nervous system.

scholarly journals Effects of anesthetics pentobarbital sodium and chloral hydrate on urine proteome

2015 ◽  
Author(s):  
Mindi Zhao ◽  
Youhe Gao
Keyword(s):  
Nervous System ◽  
Chloral Hydrate ◽  
Biomarker Discovery ◽  
Animal Experiments ◽  
Label Free ◽  
Urinary Proteins ◽  
Healthy Human ◽  
Rat Urine ◽  
Pentobarbital Sodium ◽  
Urine Proteome

Background. Urine can be a better source than blood for biomarker discovery since it accumulates many changes. The urine proteome is susceptible to many factors including anesthesia. Pentobarbital sodium and chloral hydrate are commonly used anesthetics in animal experiments. Methods. This study demonstrated effects of these two anesthetics on the rat urine proteome using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results. With anesthesia, the urinary protein-to-creatinine ratio of all rats increased two fold. The relative abundance of 22 and 23 urinary proteins were changed with pentobarbital sodium or chloral hydrate anesthesia, respectively, as determined by label-free quantification. Among these changed proteins, fifteen had been considered as candidate biomarkers such as uromodulin, sixteen had been considered stable in healthy human urine, which are more likely to be considered as potential biomarkers when changed, such as transferrin. Discussion. The pattern of changed urinary proteins provides clues to the discovery of urinary proteins regulatory mechanisms. When determining candidate biomarker, anesthetic-related effects can be excluded in future biomarker discovery studies. Since anesthetics take effects via nervous system, this study is the first to provide clues that protein handling function of kidney may possibly be regulated by nervous system.

scholarly journals Potential urinary aging markers of 20-month-old rats

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2058 ◽  
Author(s):  
Xundou Li ◽  
Youhe Gao
Keyword(s):  
Biomarker Discovery ◽  
The Body ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Human Orthologs ◽  
Human Protein Atlas ◽  
Aging Conditions ◽  
Old Rats ◽  
Spectral Counts ◽  
Altered Proteins

Urine is a very good source for biomarker discovery because it accumulates changes in the body. However, a major challenge in urinary biomarker discovery is the fact that the urinary proteome is influenced by various elements. To circumvent these problems, simpler systems, such as animal models, can be used to establish associations between physiological or pathological conditions and alterations in the urinary proteome. In this study, the urinary proteomes of young (two months old) and old rats (20 months old; nine in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between the young and old rats. Based on criteria of a fold change ≥2,P< 0.05 and identification in each rat of the high-abundance group, 33 proteins were found to be changed (15 increased and 18 decreased in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), eight proteins showed consistent changes in all rats of the groups; two of these proteins are also altered in the urinary proteome of aging humans. However, no shared proteins between our results and the previous aging plasma proteome were identified. Twenty of the 33 (60%) altered proteins have been reported to be disease biomarkers, suggesting that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs which, according to the Human Protein Atlas, are strongly expressed in the kidney, intestine, cerebellum and lung. Therefore, the urinary proteome may reflect aging conditions in these organs.

scholarly journals The potential urinary aging markers of 20-month-old rats

2015 ◽  
Author(s):  
Youhe Gao ◽  
Xundou Li
Keyword(s):  
Biomarker Discovery ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Pathological Conditions ◽  
Human Orthologs ◽  
Human Protein Atlas ◽  
Aging Conditions ◽  
Old Rats ◽  
Spectral Counts ◽  
Standard Protein

Urine is a very good source for biomarker discovery because it accumulates the changes of body. The urinary proteome is influenced by various factors, which is a major challenge in urinary biomarker discovery. To circumvent these problems, simpler systems, such as animal models, should be used to establish associations between physiological or pathological conditions and changes in the urinary proteome. In this study, the urinary proteome of young (2-month-old) and old rats (20-month-old; 9 in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between young and old rats. Based on the criteria of a fold change ≥ 2, P < 0.05 and being identified in each rat in the high abundance group, 33 proteins were changed (15 up-regulated and 18 down-regulated in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), 8 proteins were changed consistently in all rats of between the groups, 2 of which are also altered in the urinary proteome of aging humans. There are no shared proteins between our results and the previous aging plasma proteome. Twenty of the 33 (60 %) changed proteins have been reported to be disease biomarkers, which implies that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs, which are strongly expressed in the kidney, intestine, cerebellum and lung, according to the human protein ATLAS. Therefore, the urinary proteome may reflect aging conditions in these organs.

scholarly journals The potential urinary aging markers of 20-month-old rats

2015 ◽  
Author(s):  
Youhe Gao ◽  
Xundou Li
Keyword(s):  
Biomarker Discovery ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Pathological Conditions ◽  
Human Orthologs ◽  
Human Protein Atlas ◽  
Aging Conditions ◽  
Old Rats ◽  
Spectral Counts ◽  
Standard Protein

Urine is a very good source for biomarker discovery because it accumulates the changes of body. The urinary proteome is influenced by various factors, which is a major challenge in urinary biomarker discovery. To circumvent these problems, simpler systems, such as animal models, should be used to establish associations between physiological or pathological conditions and changes in the urinary proteome. In this study, the urinary proteome of young (2-month-old) and old rats (20-month-old; 9 in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between young and old rats. Based on the criteria of a fold change ≥ 2, P < 0.05 and being identified in each rat in the high abundance group, 33 proteins were changed (15 up-regulated and 18 down-regulated in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), 8 proteins were changed consistently in all rats of between the groups, 2 of which are also altered in the urinary proteome of aging humans. There are no shared proteins between our results and the previous aging plasma proteome. Twenty of the 33 (60 %) changed proteins have been reported to be disease biomarkers, which implies that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs, which are strongly expressed in the kidney, intestine, cerebellum and lung, according to the human protein ATLAS. Therefore, the urinary proteome may reflect aging conditions in these organs.

scholarly journals Application of Preparative Electrophoresis for Clinical Proteomics in Urine: Is it Feasible?

2009 ◽  
Vol 28 (4) ◽  
pp. 268-273 ◽  
Author(s):  
Jérôme Zoidakis ◽  
Ploumisti Dimitraki ◽  
Panagiotis Zerefos ◽  
Antonia Vlahou
Keyword(s):  
Protein Separation ◽  
Biomarker Discovery ◽  
Clinical Proteomics ◽  
Urinary Proteins ◽  
Preparative Electrophoresis ◽  
Disease Biomarkers ◽  
Electrophoretic Techniques ◽  
Biomarker Research ◽  
Low Molecular Weight Proteins ◽  
Proteins And Peptides

Application of Preparative Electrophoresis for Clinical Proteomics in Urine: Is it Feasible?Urine samples are easily attainable which makes them ideal substrates for biomarker research. Various techniques have been employed to unravel the urine proteome and identify disease biomarkers. Even though the presence of high abundance proteins in urine is not so pronounced as in the case of plasma, the presence of proteolytic products, many of which at low abundance, along with numerous frequently random chemical modifications, makes the analysis of urinary proteins challenging. To facilitate the detection of low abundance urinary proteins, in the study presented herein we applied two different electrophoretic techniques, preparative Lithium Dodecyl Sulfate (LDS)-PAGE in combination with 2-DE for urinary protein separation and enrichment. Our results indicate the effectiveness of this approach for the enrichment of low abundance and low molecular weight proteins and peptides in urine, and contribute towards the establishment of a urinary proteomic database. The application of this technique as a biomarker discovery tool faces several challenges: these include down-scaling of the technique, possible recompensation for the consequent expected decrease in protein resolution, by optimizing steps of the experimental workflow as well as getting a good understanding of the technical variability of the technique. Under these conditions, preparative electrophoresis can become an effective tool for clinical proteomics applications.

scholarly journals Effects of three commonly used diuretics on the urinary proteome

2013 ◽  
Author(s):  
Xundou Li ◽  
Mindi Zhao ◽  
Menglin Li ◽  
Lulu Jia ◽  
Youhe Gao
Keyword(s):  
The Body ◽  
P Value ◽  
Intragastric Administration ◽  
Protein Biomarkers ◽  
Healthy Human ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Human Orthologs ◽  
Before And After ◽  
Therapeutic Doses

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. In other words, urine is likely to be a better biomarker source than blood. However, the urinary proteome are affected by many factors. In this study, the effects of three commonly used diuretics (furosemide, hydrochlorothiazide and spirolactone ) on the urinary proteome were analyzed in rats. Urine samples were collected before and after the intragastric administration of diuretics at therapeutic doses and analyzed using LC-MS/MS. Based on quantification by Progenesis LC-MS software, there are 7, 5 and 2 proteins with the p value ≤0.05, a fold change ≥2, a spectral count ≥5 and FDR ≤1%, respectively. Most their human orthologs were considered to be stable in the healthy human urinary proteome. 10 of the 14 proteins have been reported as disease biomarkers in previous studies. So the effects of diuretics should be given more attention in future urinary protein biomarkers studies. The effects of diuretics on urinary proteome are different which can provide clues to elucidate the mechanisms of the diuretics.

scholarly journals The potential urinary aging markers of 20-month-old rats

2015 ◽  
Author(s):  
Youhe Xundou Gao ◽  
Xundou Xundou Li
Keyword(s):  
Biomarker Discovery ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Pathological Conditions ◽  
Human Orthologs ◽  
Human Protein Atlas ◽  
Aging Conditions ◽  
Old Rats ◽  
Spectral Counts ◽  
Standard Protein

Urine is a very good source for biomarker discovery because it accumulates the changes of body. The urinary proteome is influenced by various factors, which is a major challenge in urinary biomarker discovery. To circumvent these problems, simpler systems, such as animal models, should be used to establish associations between physiological or pathological conditions and changes in the urinary proteome. In this study, the urinary proteome of young (2-month-old) and old rats (20-month-old; 9 in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between young and old rats. Based on the criteria of a fold change ≥ 2, P < 0.05 and being identified in each rat in the high abundance group, 33 proteins were changed (15 up-regulated and 18 down-regulated in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), 8 proteins were changed consistently in all rats of between the groups, 2 of which are also altered in the urinary proteome of aging humans. There are no shared proteins between our results and the previous aging plasma proteome. Twenty of the 33 (60 %) changed proteins have been reported to be disease biomarkers, which implies that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs, which are strongly expressed in the kidney, intestine, cerebellum and lung, according to the human protein ATLAS. Therefore, the urinary proteome may reflect aging conditions in these organs.

scholarly journals Effects of three commonly used diuretics on the urinary proteome

2013 ◽  
Author(s):  
Xundou Li ◽  
Mindi Zhao ◽  
Menglin Li ◽  
Lulu Jia ◽  
Youhe Gao
Keyword(s):  
The Body ◽  
P Value ◽  
Intragastric Administration ◽  
Protein Biomarkers ◽  
Healthy Human ◽  
Disease Biomarkers ◽  
Urinary Proteome ◽  
Human Orthologs ◽  
Before And After ◽  
Therapeutic Doses

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. In other words, urine is likely to be a better biomarker source than blood. However, the urinary proteome are affected by many factors. In this study, the effects of three commonly used diuretics (furosemide, hydrochlorothiazide and spirolactone ) on the urinary proteome were analyzed in rats. Urine samples were collected before and after the intragastric administration of diuretics at therapeutic doses and analyzed using LC-MS/MS. Based on quantification by Progenesis LC-MS software, there are 7, 5 and 2 proteins with the p value ≤0.05, a fold change ≥2, a spectral count ≥5 and FDR ≤1%, respectively. Most their human orthologs were considered to be stable in the healthy human urinary proteome. 10 of the 14 proteins have been reported as disease biomarkers in previous studies. So the effects of diuretics should be given more attention in future urinary protein biomarkers studies. The effects of diuretics on urinary proteome are different which can provide clues to elucidate the mechanisms of the diuretics.

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