Gene chromosomal organization and expression in cultured human neurons exposed to cocaine and HIV-1 proteins gp120 and tat: drug abuse and NeuroAIDS.
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 < or = 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 that 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.
Shapshak
Paul
P
Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, FL 33136, USA. pshapsha@med.miami.edu
Duncan
Robert
R
Nath
Avindra
A
Turchan
Jadwiga
J
Pandjassarame
Kangueane
K
Rodriguez
Hector
H
Duran
Elda Margarita
EM
Ziegler
Fabiana
F
Amaro
Eric
E
Lewis
Apple
A
Rodriguez
Alejandro
A
Minagar
Alireza
A
Davis
Wade
W
Seth
Raman
R
Elkomy
Fatten F
FF
Chiappelli
Francesco
F
Kazic
Toni
T
D015526:AIDS Dementia Complex / Q000473:pathology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure*; D003042:Cocaine / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods; D004660:Encephalitis / Q000378:metabolism; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D015233:Models, Statistical; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
D015699:HIV Envelope Protein gp120; D003042:Cocaine