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Series GSE5080

Query DataSets for GSE5080

Status

Public on Jun 14, 2007

Title

Harmane Alters the Expression of a Subset of Genes with Diverse Functions in Primary Human Astrocytes

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

Essential tremor (ET) is the most common movement disorder in adults, but little is known about the molecular mechanisms underlying ET pathogenesis. Harmane is a member of a group of tremorogenic chemicals. In humans, increased blood harmane concentration is associated with increased risk of ET. Astrocytes are essential for brain function, and astrocyte dysfuctions are associated with many neurodegenerative diseases. Therefore, we identified the molecular targets of harmane in primary human astrocytes by using microarray gene expression profiling and computational analysis algorithms. We found that harmane altered the expression of a limited number of genes encoding diverse functions. Notably, the transcript levels of two GABA receptors and a GABA transporter were altered by harmane, consistent with previous evidence suggesting that the GABAergic neurotransmission system may be disrupted in ET. Also, we found that the transcript levels of two prominent proinflammatory enzymes, the inducible nitric oxide synthase NOS2A and the cyclooxygenase COX2, and 10 other targets of the proinflammatory IFN-gamma signaling pathway were up-regulated by harmane. These results together raise the possibility that perturbation of the expression of functions involved in neurotransmission and inflammatory activation of astrocytes might be important mechanisms underlying the neurotoxicity of harmane and ET pathogenesis.
Keywords: treatment comparison

Overall design

Primary human astrocytes (passage 4) were treated with or without 1 uM harmane for 7 days. Total RNA was extracted by using TRIzol reagent (GIBCOBRL Life Technologies). The quality of RNA was high as assessed by measuring absorbance at 260 and 280 nm, by gel electrophoresis, and by the quality of microarray data (see below). We isolated RNA from three independent batches of human astrocytes, which were from different subjects. No identifiable information from these subjects was available, in keeping with the guidelines on human subjects. Three independent batches of astrocytes from three different subjects, not the same subject, were used to ensure that our data and conclusions would not totally rely on one unidentified subject, who may have experienced influential environmental or genetic conditions. The synthesis of cDNAs and biotin-labeled cRNAs were carried out exactly as described in the Affymetrix GeneChip Expression Analysis Technical Manual (2000). The human genome U133 plus 2.0 arrays were purchased from Affymetrix, Inc. Probe hybridization and data collection were carried out by the Columbia University Affymetrix GeneChip processing center. Initial data analysis was performed by using the Affymetrix Microarray suite.

Contributor(s)

Zhang L, Mense SM

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Submission date

Jun 14, 2006

Last update date

Mar 25, 2019

Contact name

Sarah Mense

E-mail(s)

smm2123@columbia.edu