Quantitative proteomic analysis of HIV-1 Tat-induced dysregulation in SH-SY5Y neuroblastoma cells

ABSTRACT: Despite affecting up to 70% of HIV+ patients and being the leading cause of dementia in patients under 40 years, the molecular mechanisms involved in the onset of HAND are not well understood. To address this, we performed SILAC-based quantitative proteomic analysis on HIV-Tat treated SH-SY5Y neuroblastoma cells. Isolated protein was fractionated by SDS-PAGE and analysed by nLC-MS/MS on an Orbitrap Velos. Using MaxQuant, we identified and quantitation 3077 unique protein groups. Statistical analysis identified 407 differentially regulated proteins, of which 29 were identified as highly significantly and stably dysregulated using an additional standard deviation-based cutoff. GO-term analysis shows dysregulation in both protein translation machinery as well as cytoskeletal regulation which have both been implicated in other dementias. In addition, several key cytoskeletal regulatory proteins such as ARHGEF17, the Rho GTPase, SHROOM3 and CMRP1 are down-regulated. Together, we show that HIV-Tat can dysregulate neuronal cytoskeletal regulatory proteins which could lead to the major HAND clinical manifestation - synapse loss.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jonathan Blackburn  

PROVIDER: MSV000083590 | MassIVE | Mon Mar 18 06:21:00 GMT 2019

SECONDARY ACCESSION(S): PXD004241

REPOSITORIES: MassIVE