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Alteration of gene expression profile in HEK293 cells treated with proteasome inhibitor epoxomicin

ABSTRACT: The objective of this study is to identify the genes that are up-regulated amid proteasome dysfunction to facilitate the discovery of proteolytic pathways that are activated as a compensatory response to proteasome inhibition. Proteasome is a large multi-component proteolytic complex in the cell. It is responsible for the constitutive turn-over of many cellular proteins as well as the degradation of oxidized and/or unfolded proteins. With such a fundamental role in the cell, disruption of proteasome understandably can lead to disastrous outcome. Oxidative stress has been postulated as the driving mechanism for aging. Oxidatively modified proteins, which usually have lost their activity, require immediate removal by proteasome to maintain normal cellular function. Dysfunction of proteasome has also been linked to neuro-degenerative diseases such as Alzheimer’s and Parkinson’s diseases, those that are most commonly seen in aged population. There is more than one proteolytic pathway in the cell, and it has been reported that obstruction of any one of these pathways may enhance the activity of the others. Proteasomal function has been found to have decreased during aging, prompting researchers to hypothesize that failure to remove oxidized proteins may play an important role in aging. It would be interesting to determine the other proteolytic pathways that are activated after proteasome inhibition by a relatively specific inhibitor epoxomicin to help understand their roles in aging processes. Keywords: time course, proteasome, inhibitor, oxidative stress, epoxomicin

ORGANISM(S): Homo sapiens

PROVIDER: GSE14429 | GEO | 2009/01/15

SECONDARY ACCESSION(S): PRJNA111757

REPOSITORIES: GEO

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Transcription profiling by array of human HEK293 cells treated with the proteasome inhibitor epoxomicin

Project description:The objective of this study is to identify the genes that are up-regulated amid proteasome dysfunction to facilitate the discovery of proteolytic pathways that are activated as a compensatory response to proteasome inhibition. Proteasome is a large multi-component proteolytic complex in the cell. It is responsible for the constitutive turn-over of many cellular proteins as well as the degradation of oxidized and/or unfolded proteins. With such a fundamental role in the cell, disruption of proteasome understandably can lead to disastrous outcome. Oxidative stress has been postulated as the driving mechanism for aging. Oxidatively modified proteins, which usually have lost their activity, require immediate removal by proteasome to maintain normal cellular function. Dysfunction of proteasome has also been linked to neuro-degenerative diseases such as Alzheimer?¢¬Ä¬ôs and Parkinson?¢¬Ä¬ôs diseases, those that are most commonly seen in aged population. There is more than one proteolytic pathway in the cell, and it has been reported that obstruction of any one of these pathways may enhance the activity of the others. Proteasomal function has been found to have decreased during aging, prompting researchers to hypothesize that failure to remove oxidized proteins may play an important role in aging. It would be interesting to determine the other proteolytic pathways that are activated after proteasome inhibition by a relatively specific inhibitor epoxomicin to help understand their roles in aging processes. Experiment Overall Design: Human embryonic kidney cells (HEK293) were untreated or treated with 1 uM epoxomicin for 1 and 6 hours. Total RNA was extracted for gene expression profiling using Affymetrix human genome U133 2.0 plus chip. A quadrupliate was prepared for each treatment. Experiment Overall Design: contributor: NHLBI Gene Expression Core Facility

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