Synaptic proteins linked to HIV-1 infection and immunoproteasome induction: Proteomic analysis of human synaptosomes

Benjamin Gelman, Trung P. Nguyen

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Infection of the central nervous system with human immunodeficiency virus type 1 (HIV-1) can produce morphological changes in the neocortical synaptodendritic arbor that are correlated with neurocognitive impairment. To determine whether HIV-1 infection influences the protein composition of human synapses, a proteomic study of isolated nerve endings was undertaken. Synaptosomes from frontal neocortex were isolated using isopyknic centrifugation from 19 human brain specimens. Purity and enrichment were assessed by measuring pre- and postsynaptic protein markers. Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to screen for proteins differentially expressed in HIV/AIDS. The concentrations of 31 candidate protein spots were potentially abnormal in HIV-infected decedents with HIV encephalitis and/or increased expression of immunoproteasome subunits. Immunoblots showed that the concentration of some of them was related to HIV-1 infection of the brain and immunoproteasome (IPS) induction. Synapsin 1b and stathmin were inversely related to brain HIV-1 load; 14-3-3ζ and 14-4-4ε proteins were higher in subjects with HIV-1 loads. Perturbed synaptosome proteins were linked with IPS subunit composition, and 14-3-3ζ was histologically colocalized with IPS subunits in stained neocortical neurons. Proteomics illustrates that certain human proteins within the synaptic compartment are involved with changes in the synaptodendritic arbor and neurocognitive impairment in HIV-1-infected people.

Original languageEnglish (US)
Pages (from-to)92-102
Number of pages11
JournalJournal of NeuroImmune Pharmacology
Volume5
Issue number1
DOIs
StatePublished - Mar 2010

Fingerprint

Synaptosomes
Virus Diseases
Proteomics
HIV-1
Proteins
HIV
Brain
Stathmin
Synapsins
Central Nervous System Infections
Nerve Endings
Neocortex
Electrophoresis, Gel, Two-Dimensional
Encephalitis
Centrifugation
Synapses
Mass Spectrometry
Acquired Immunodeficiency Syndrome
Lasers
Neurons

Keywords

  • 14-3-3
  • Encephalitis
  • Immunoproteasome
  • Proteomic
  • Synapsin
  • Synaptosome

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

Cite this

Synaptic proteins linked to HIV-1 infection and immunoproteasome induction : Proteomic analysis of human synaptosomes. / Gelman, Benjamin; Nguyen, Trung P.

In: Journal of NeuroImmune Pharmacology, Vol. 5, No. 1, 03.2010, p. 92-102.

Research output: Contribution to journalArticle

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