| Publication Abstract Display | | Type: Published Abstract | | Title: Short and long term effect of methamphetamine withdrawal: Proteomic profiling of plasma from HIV-infected patients. | | Authors: Ciborowski P, Pottiez G, Jagadish T, Grant I, Ellis R, Letendre S, Fox H | | Year: 2010 | | Publication: 10th International Symposium on NeuroVirology | | Volume: Issue: Pages: | | Abstract:INTRODUCTION: Use of methamphetamine (METH) with concomitant
HIV-1 infection can increase the risk of central nervous system (CNS)
injury. We still lack reliable biomarkers that reflect the molecular
mechanisms underlying the neurocognitive impairment associated of
either of these diseases. We postulated that application of unbiased
proteomic profiling of plasma could lead to new markers of disease and
insights into neuropathogenic disease processes.
PATIENT COHORT: Samples were provided by HIV Neurobehavioral
Research Programs (HNRP) at the University of California San Diego which
have been investigating the impact of METH on the brain in HIV-infected
and uninfected individuals. We used samples from the same individual at
2 time points. Four cohorts of 8 samples each were used. Three cohorts
consisted of HIV-infected patients with i). Persistent METH use; ii). Longterm
METH abstinence; iii). Short-term METH abstinence. Fourth cohort,
control, consists of HIV- and METH- individuals.
EXPERIMENTAL APPROACH: We selected MudPIT with 8-plex iTRAQ
approach as primary method of profiling. Plasma samples were
immundepleted from 14 most abundant proteins, digested with trypsin,
labeled with iTRAQ labels fractionated using isoelectric focusing mode
(first dimension) and further fractionated using RP-HPLC. For mass
spectrometry data acquisition we used an ABI 4800 MALDI-TOF/TOF
instrument equipped with Protein Pilot software for database search
and peptide/protein quantitation.
RESULTS: Summarizing, we have identified and quantitated 450 proteins
belonging to various functional classes such as regulatory, structural,
enzymes etc. Preliminary analysis showed that among others levels of
proteins such as plasminogen isoform 1, guanine nucleotide regulatory
protein, vitamin D binding protein and ceruloplasmin circulating in
plasma are changed by METH. Differential expression of these proteins
will provide new insights into host's response to the viral infection.
To make these proteins relevant as diagnostic biomarkers larger cohorts
are needed. |
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