Related Experiment Video
Updated: Aug 4, 2026
Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
Published on: February 7, 2018
Ets-2 is induced by oxidative stress and sensitizes cells to H(2)O(2)-induced apoptosis: implications for Down's
E Sanij1, T Hatzistavrou, P Hertzog
1Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia.
Abstract:
An elevated production of hydrogen peroxide mediates the increased rate of apoptosis of cells derived from individuals with Down's syndrome. The mechanism via which this occurs is unknown. Here we show that Ets-2, a transcription factor located on human chromosome 21 and already overexpressed in multiple tissues in Down syndrome (DS, trisomy 21), is induced by low concentrations of hydrogen peroxide. Moreover, cells with an imbalance in the antioxidant enzymes SOD-1/GPX-1, such as occurs in DS through the overexpression of the chromosome 21 gene SOD-1, also results in increased Ets-2 expression. The increase in Ets-2 expression is dependent on mRNA transcription. Importantly, we further demonstrate that 3T3 fibroblasts that overexpress Ets-2 are sensitized to hydrogen peroxide-induced apoptosis. These data implicate Ets-2 in the regulation of oxidant-induced apoptosis and provide a possible rationale for both the (5- to 7-) fold increase in Ets-2 protein level in DS tissues, above the expected gene dosage of 1.5-fold, and the elevated rate of apoptosis in DS cells.
Insights
Down syndrome (DS) cells show increased apoptosis due to hydrogen peroxide. Researchers found that the Ets-2 gene, overexpressed in DS, is induced by hydrogen peroxide and sensitizes cells to apoptosis, explaining DS cell death.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Individuals with Down syndrome (DS, trisomy 21) exhibit elevated apoptosis.
- Hydrogen peroxide (H2O2) is implicated in this increased cell death, but the underlying mechanism remains unclear.
- Ets-2, a transcription factor on human chromosome 21, is overexpressed in DS tissues.
Purpose of the Study:
- To elucidate the mechanism linking hydrogen peroxide, Ets-2, and apoptosis in Down syndrome.
- To investigate the role of Ets-2 in hydrogen peroxide-induced apoptosis.
Main Methods:
- Investigated the induction of Ets-2 by low concentrations of hydrogen peroxide.
- Examined Ets-2 expression in cells with imbalanced antioxidant enzymes (SOD-1/GPX-1), mimicking DS conditions.
- Assessed the dependence of Ets-2 increase on mRNA transcription.
- Overexpressed Ets-2 in 3T3 fibroblasts and tested their sensitivity to hydrogen peroxide-induced apoptosis.
Main Results:
- Low concentrations of hydrogen peroxide induce Ets-2 expression.
- Imbalance in SOD-1/GPX-1, as seen in DS due to SOD-1 overexpression, also increases Ets-2 expression.
- Ets-2 expression increase is dependent on mRNA transcription.
- Fibroblasts overexpressing Ets-2 show increased sensitivity to hydrogen peroxide-induced apoptosis.
Conclusions:
- Ets-2 is implicated in the regulation of oxidant-induced apoptosis.
- Ets-2 overexpression, potentially triggered by hydrogen peroxide and antioxidant enzyme imbalance, provides a mechanistic link to elevated apoptosis in Down syndrome cells.
- This finding helps explain the significantly higher Ets-2 protein levels observed in DS tissues.
More Related Videos
13:59A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
Published on: August 12, 2018
10:00Induction and Analysis of Oxidative Stress in Sleeping Beauty Transposon-Transfected Human Retinal Pigment Epithelial Cells
Published on: December 11, 2020
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:00Cellular Injury I: Introduction
01:21Cellular Injury II: Classification
01:22Cellular Injury V: Apoptosis and Autophagy
01:26Type II Diabetes I: Introduction
01:24Type II Diabetes II: Pathophysiology