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Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

Abstract The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.
PMID
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Authors

Mayor MeshTerms

Drug Discovery

Molecular Targeted Therapy

Keywords

Obesity

human liver proteome

metabolic syndrome

oxidative stress

protein biomarkers

Journal Title journal of enzyme inhibition and medicinal chemistry
Publication Year Start




PMID- 28274171
OWN - NLM
STAT- MEDLINE
DA  - 20170309
DCOM- 20170317
LR  - 20170317
IS  - 1475-6374 (Electronic)
IS  - 1475-6366 (Linking)
VI  - 32
IP  - 1
DP  - 2017 Dec
TI  - Differential representation of liver proteins in obese human subjects suggests
      novel biomarkers and promising targets for drug development in obesity.
PG  - 672-682
LID - 10.1080/14756366.2017.1292262 [doi]
AB  - The proteome of liver biopsies from human obese (O) subjects has been compared to
      those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE).
      Differentially represented proteins were identified by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based
      peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to
      electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products 
      common to all of the liver biopsies were identified within 65 spots, among which 
      25 ones were differently represented between O and NO subjects. In particular,
      over-representation of short-chain acyl-CoA dehydrogenase,
      Delta(3,5)-Delta(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase,
      glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, 
      peroxiredoxin I, protein DJ-1, catalase, alpha- and beta-hemoglobin subunits,
      3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine
      biosynthesis-like domain-containing protein and a form of fatty acid-binding
      protein, together with downrepresentation of glutamate dehydrogenase, glutathione
      S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein
      A-I, was associated with the obesity condition. Some of these metabolic enzymes
      and antioxidant proteins have already been identified as putative diagnostic
      markers of liver dysfunction in animal models of steatosis or obesity, suggesting
      additional investigations on their role in these syndromes. Their differential
      representation in human liver was suggestive of their consideration as obesity
      human biomarkers and for the development of novel antiobesity drugs.
FAU - Caira, Simonetta
AU  - Caira S
AD  - a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council
      , Naples , Italy.
FAU - Iannelli, Antonio
AU  - Iannelli A
AD  - b Departement de Chirurgie Digestive , Centre Hospitalier Universitarie de Nice ,
      Nice , France.
FAU - Sciarrillo, Rosaria
AU  - Sciarrillo R
AD  - c Dipartimento di Scienze e Tecnologie , Universita degli Studi del Sannio ,
      Benevento , Italy.
FAU - Picariello, Gianluca
AU  - Picariello G
AD  - d Institute of Food Sciences, National Research Council , Avellino , Italy.
FAU - Renzone, Giovanni
AU  - Renzone G
AD  - a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council
      , Naples , Italy.
FAU - Scaloni, Andrea
AU  - Scaloni A
AD  - a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council
      , Naples , Italy.
FAU - Addeo, Pietro
AU  - Addeo P
AD  - e Service de Chirurgie Hepatique, Pancreatique, Biliaire et Transplantation, Pole
      des Pathologies Digestives, Hepatiques et de la Transplantation, Hopital de
      Hautepierre , Universite de Strasbourg, Hopitaux Universitaires de Strasbourg ,
      Strasbourg , France.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Enzyme Inhib Med Chem
JT  - Journal of enzyme inhibition and medicinal chemistry
JID - 101150203
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Proteins)
RN  - 0 (Proteome)
SB  - IM
MH  - Adult
MH  - Anti-Obesity Agents/chemistry/*pharmacology
MH  - Biomarkers/analysis
MH  - *Drug Discovery
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Female
MH  - Humans
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - *Molecular Targeted Therapy
MH  - Obesity/*drug therapy/*metabolism
MH  - Proteins/antagonists & inhibitors/chemistry/*metabolism
MH  - Proteome/drug effects
OTO - NOTNLM
OT  - Obesity
OT  - human liver proteome
OT  - metabolic syndrome
OT  - oxidative stress
OT  - protein biomarkers
EDAT- 2017/03/10 06:00
MHDA- 2017/03/18 06:00
CRDT- 2017/03/10 06:00
AID - 10.1080/14756366.2017.1292262 [doi]
PST - ppublish
SO  - J Enzyme Inhib Med Chem. 2017 Dec;32(1):672-682. doi:
      10.1080/14756366.2017.1292262.

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