Analyses of Methamphetamine-Exposed and HIV- infected Human Monocyte-Derived Macrophages (hMDM)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE160323 | GEO | 2021/09/28
REPOSITORIES: GEO
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Project description:Macrophages are involved in the immunological response to inflammatory and infectious agents, including Human Immunodeficiency Virus type 1 (HIV-1) infection. They are a primary targets of the virus and facilitate transfer across the blood brain barrier into the central nervous system. In the presence of toxic substances, such as methamphetamine (Meth), the protective functions of macrophages are further impaired. It has been shown that both HIV-1 infection and Meth induce changes in the proteome of macrophages. Therefore, in the presented study we employed a nano-liquid chromatography (nanoLC)-SWATH mass spectrometry (MS) approach to detect and quantify changes on proteome level that are induced in human monocyte derived macrophages (hMDM) that were exposed to Meth before or after HIV infection. As we focused in this study on actin and a cluster of Ras-related proteins (Rab), we selected the following proteins: actin (UniProt P60709), Ras-related protein Rab-1A (UniProt P62820), Ras-related protein Rab-2A (UniProt P61019), Ras-related protein Rab-4B (UniProt P61018), Ras-related protein Rab-7A (UniProt P51149), Ras-related protein Rab-9A (UniProt P51151), Ras-related protein Rab-11 (UniProt P62491), Ras-related protein Rab-14 (UniProt P61106), Ras-related protein Rab-22A (UniProt Q9UL26), Ras-related protein Rab-24 (UniProt Q969Q5), Ras-related protein Rab-37 (UniProt Q96AX2) for further validation, which we performed using liquid chromatography-multiple reaction monitoring (LC-MRM) MS technique. The MRM data from this study, along with LC-MRM analysis and data processing parameters, were separately described and deposited in PASSEL repository with accession number PASS01591.
2022-05-19 | PXD023291 | Pride
Project description:Analyses of Methamphetamine-Exposed and HIV- infected Human Monocyte-Derived Macrophages (hMDM)
| PRJNA672944 | ENA
Project description:Our goal was to examine whether the HIV Tat peptide, which is usually secreted from infected cells and has the potential to act in other cell types, alters gene expression in the Central Nervous System, and whether a drug abuse co-morbidity, in the case Methamphetamine, can play a role in further modifying gene expression. In order to address the effects of HIV Tat and Methamphetamine, alone and combined, we used an in vivo mouse model that has been described to mimic several aspects of neuroHIV, including changes in inflammatory markers, and decreased expression of dopamine receptors. These animals are transgenic mice, which upon treatment with with doxycycline for 10 days, express TAT protein under the control of the glial fibrilary associated protein (GFAP) promoter in the brain. They were treated with Meth and Saline for identification of gene expression changes that result from Tat or Methamphetamine alone, or from their interaction. There was an overall suppression of gene expression by Methamphetamine, in Tat- mice. The expression of Tat caused most Meth-induced changes to remain at control levels.
2018-03-17 | GSE111925 | GEO
Project description:Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge.
2010-03-04 | GSE17665 | GEO
Project description:Analysis of the human monocyte-derived macrophage (hMDM) transcriptional response to L. pneumophila infection at 8 hours post-infection We used microarrays to probe the hMDM transcriptional response to wild type L. pneumophila AA100 infection and its isogenic ankB and T2SS mutants. We identified up-regulation of innate immunity pathways and down-regulation of protein translation pathways hMDMs were isolated from healthy donors and infected with L. pneumophila AA100 and its isogenic ankB and T2SS mutants for 8 h prior to isolation of total RNA and hybridization to Affymetrix microarrays.
2014-09-19 | E-GEOD-61535 | biostudies-arrayexpress
Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall omic response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals. For each sample, 20 virgin male flies were used to extract the mRNA. Three replicates were produced for each treatments. Two treatments were produced (control VS 0.6% 24 h meth-fed).
2010-10-30 | E-GEOD-16198 | biostudies-arrayexpress
Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations. To study the effects of chronic METH effects on the brain
2011-11-15 | E-GEOD-33707 | biostudies-arrayexpress
Project description:Methamphetamine (METH) is a powerful stimulant that has caused addiction (compulsive drug seeking and taking behavior) in millions of people world-wide. METH abuse is also associated with negative impact on the brain. One feature of addiction is uncontrollable drug seeking despite adverse consequences and becomes habitual. To mimic this in a rat model, rats with a history of METH use are given the opportunity to earn METH accompanied by aversive shocks on their feet. Rats that continue to take METH are shock-resistant (SR) and rats that reduce their METH intake are shock-sensitive (SS ).Rats that self-administered saline are controls (CT). In addition, we used controls for shock paradigm. For this purpose, when METH SA rat received a shock, the saline SA rat was also shocked. The separate groups of rats that were yoked (Y) to the corresponding METH shock-resistant (SR) and shock-sensitive (SS) rats are termed YSR and YSS, respectively.
2023-02-01 | GSE203268 | GEO
Project description:This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10d, 3mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change>1.5, p<0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. This study addresses how HIV-1 and methamphetamine comorbidities affect cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation.
2016-05-23 | GSE64158 | GEO
Project description:Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs, which is known to cause brain damage from repeated exposure on human. Herein, a proteomic study was applied to evaluate METH-induced brain protein dynamics following a two-week chronic regimen of escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantitation was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in hippocampal proteome, 7 in olfactory bulb proteome) were shown a significant alteration as a result of exposure of rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 of were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis.
2016-04-21 | PXD000915 | Pride