Isobaric tagging-based quantification by mass spectrometry of differentially regulated proteins in synaptosomes of HIV/gp120 transgenic mice: implications for HIV-associated neurodegeneration.

Experimental Neurology
Sugato BanerjeeStuart A Lipton

Abstract

HIV/gp120 transgenic mice manifest neuropathological features similar to HIV-associated neurocognitive disorders (HAND) in humans, including astrogliosis, microglia activation, and decreased neuronal synapses. Here, proteomic screening of synaptosomes from HIV/gp120 transgenic mice was conducted to determine potential neuronal markers and drug targets associated with HAND. Synaptosomes from 13 month-old wild-type (wt) and HIV/gp120 transgenic mouse cortex were subjected to tandem mass tag (TMT) labeling and subsequent analysis using an LTQ-Orbitrap mass spectrometer in pulsed-Q dissociation (PQD) mode for tandem mass spectrometry (MS/MS). A total of 1301 proteins were identified in both wt and HIV/gp120 transgenic mice. Three of the most differentially-regulated proteins were validated by immunoblotting. To elucidate putative pathways associated with the proteomic profile, 107 proteins manifesting a ≥1.5 fold change in expression were analyzed using a bioinformatics pathway analysis tool. This analysis revealed direct or indirect involvement of the phosphotidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, a well-known neuronal survival pathway. Immunoblots confirmed a lower phospho (p)Akt/Akt ratio in synaptosomes fr...Continue Reading

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Citations

Mar 12, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Lerna UzasciRobert Cotter
Jun 3, 2015·Proteomics. Clinical Applications·Maire Rose Donnelly, Pawel Ciborowski
May 31, 2013·Neuron·Tomohiro NakamuraStuart A Lipton
Nov 11, 2016·Oxidative Medicine and Cellular Longevity·Alexander V IvanovMaria G Isaguliants
Jun 5, 2014·Molecular & Cellular Proteomics : MCP·Monika Zaręba-KoziołMaciej Lalowski
Mar 16, 2018·Neurochemical Research·Matthew V GreenStanley A Thayer

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