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Clinical Proteomics

, 9:11

First Online: 07 September 2012Received: 12 August 2011Accepted: 15 February 2012

Abstract

BackgroundPathogenesis of liver damage in patients with HIV and HCV co-infection is complex and multifactorial. Although global awareness regarding HIV-1-HCV co-infection is increasing little is known about the pathophysiology that mediates the rapid progression to hepatic disease in the co-infected individuals.

ResultsIn this study, we investigated the proteome profiles of peripheral blood mononuclear cells from HIV-1 mono-, HCV mono-, and HIV-1-HCV co-infected patients. The results of high-resolution 2D gel electrophoresis and PD quest software quantitative analysis revealed that several proteins were differentially expressed in HIV-1, HCV, and HIV-1-HCV co-infection. Liquid chromatography-mass spectrometry and Mascot database matching LC-MS-MS analysis successfully identified 29 unique and differentially expressed proteins. These included cytoskeletal proteins tropomyosin, gelsolin, DYPLSL3, DYPLSL4 and profilin-1, chaperones and co-chaperones HSP90-beta and stress-induced phosphoprotein, metabolic and pre-apoptotic proteins guanosine triphosphate GTP-binding nuclear protein Ran, the detoxifying enzyme glutathione S-transferase GST and Rho GDP-dissociation inhibitor Rho-GDI, proteins involved in cell prosurvival mechanism, and those involved in matrix synthesis collagen binding protein 2 CBP2. The six most significant and relevant proteins were further validated in a group of mono- and co-infected patients n = 20 at the transcriptional levels.

ConclusionsThe specific pro- and anti- apoptotic protein signatures revealed in this study could facilitate the understanding of apoptotic and protective immune-mediated mechanisms underlying HIV-1 and HCV co-infection and their implications on liver disease progression in co-infected patients.

KeywordsHIV-1 HCV HIV-1-HCV 2D-GE Mass spectrometry Pro- and anti-apoptotic fingerprinting Proteomics AbbreviationsABAmmonium bicarbonate

ACNAcetonitrile

AFPα-fetoprotein

AIDSAcquired immunodeficiency Syndrome

CBP2Collagen binding protein 2

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

GDPGuanosine diphosphate

GTPGuanosine triphosphate

HCVHepatitis C virus

HCCHepatocellular carcinoma

HIV-1Human immunodeficiency virus type 1

HPLCHigh-performance liquid chromatography

HSP90-betaHeat shock protein 90 beta

IEFIsoelectric focusing

IPIInternational Protein Index

LC-MS-MSLiquid chromatography-mass spectrometry and Mascot database

NADPHNicotinamide adenine dinucleotide phosphate

PBMCPeripheral blood mononuclear cells

Rho-GDI-1Rho GDP-dissociation inhibitor 1

ROSReactive oxygen species

STIP-1Stress-induced phosphoprotein 1

SDS-PAGESodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Electronic supplementary materialThe online version of this article doi:10.1186-1559-0275-9-11 contains supplementary material, which is available to authorized users.

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Autor: Nawal M Boukli - Vivekananda Shetty - Luis Cubano - Martha Ricaurte - Jordana Coelho-dos-Reis - Zacharie Nickens - Punit S

Fuente: https://link.springer.com/







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