Gene chromosomal organization and expression in cultured human neurons exposed to cocaine and HIV-1 proteins gp120 and tat: Drug abuse and NeuroAIDS

Paul Shapshak, Robert Duncan, Avindra Nath, Jadwiga Turchan, Pandjassarame Kangueane, Hector Rodriguez, E. Margarita Duran, Fabians Ziegler, Eric Amaro, Apple Lewis, Alejandro Rodriguez, Alireza Minagar, Wade Davis, Raman Seth, Fatten F. Elkomy, Francesco Chiappelli, Toni Kazic

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

As a model for Neuropsychiatric dysfunction in NeuroAIDS due to HIV-1 infection and drug abuse, we analyzed gene expression in human neurons treated with cocaine and HIV-1 proteins tat and envelope (env). One-way ANOVA showed statistically significant genes among the treatment groups (p ≤ 0.0005). The identified genes were then subjected to a "stepwise" analysis using a repeated measures ANOVA to discover genes with parallel response group profiles across the treatment conditions. These groups were then analyzed using a repeated measures ANOVA to assess treatment main effects and gene-by-treatment interactions within groups. One-way ANOVA produced 35 genes that were significantly associated across all treatment conditions. Factorial analysis of each gene found statistically significant differences: 30 - tat, 17 - cocaine, 10 - env, 6 - tat/env, 6 - coc/env, and 4 - coc/tat Analyses across genes found three sets of four genes, one set of three genes, and three sets of two genes with parallel profiles. Identified genes had functions included signaling, immune related, and transcription control. The genes were not stochastically arranged on the chromosomes, were in proximity to each other, and to other genes involved in neuropsychiatric diseases. We hypothesize that these genes fall in transcriptionally isolated groups and mat abused drugs and HIV-1 proteins trigger transcription overload, coerced expression that may result in damage to the chromosome's control and organization of chromatin transcription machinery.

Original languageEnglish
Pages (from-to)1774-1793
Number of pages20
JournalFrontiers in Bioscience
Volume11
Issue number2 P.1591-2006
StatePublished - Feb 23 2006
Externally publishedYes

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Keywords

  • Affymetrix
  • AIDS
  • Ariadne Pathways Assist
  • Bioinformatics
  • Chromosome Damage
  • Cocaine
  • Coerced Transcription
  • Culture
  • Encephalitis
  • Gene Expression
  • gp120
  • HIV Associated Dementia (HAD)
  • HIV-1
  • Human
  • Microarray
  • Neuron
  • Tat
  • Transcription Isolation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Shapshak, P., Duncan, R., Nath, A., Turchan, J., Kangueane, P., Rodriguez, H., Duran, E. M., Ziegler, F., Amaro, E., Lewis, A., Rodriguez, A., Minagar, A., Davis, W., Seth, R., Elkomy, F. F., Chiappelli, F., & Kazic, T. (2006). Gene chromosomal organization and expression in cultured human neurons exposed to cocaine and HIV-1 proteins gp120 and tat: Drug abuse and NeuroAIDS. Frontiers in Bioscience, 11(2 P.1591-2006), 1774-1793.