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| Status |
Public on Jan 30, 2014 |
| Title |
Oxidative stress induces mitochondrial dysfunction and a protective unfolded protein response in RPE cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
How retinal pigmented epithelial (RPE) cells degenerate from oxidative stress in age-related macular degeneration (AMD) is incompletely understood. The study's intent was to identify key cytoprotective pathways activated by oxidative stress, and to determine the extent of their protection. Immunohistochemistry was used to identify the unfolded protein response (UPR) and mitochondria in the RPE of AMD samples. Maculas with early AMD had prominent IRE1α, but minimal mitochondrial TOM20 immunolabeling in mildly degenerated RPE. RPE cells treated with cigarette smoke extract (CSE), by microarray analysis, had over-represented genes involved in the antioxidant and unfolded protein response, and mitochondrial location. CSE induced the UPR sensors IRE1α, p-PERK, and ATP6, which activated CHOP. CHOP knockdown compromised cell viability after CSE exposure. At the same CSE doses, mitochondria generated superoxide anion and produced less ATP. In mice given intravitreal CSE, the RPE had increased IRE1α and decreased ATP, which elicited RPE epithelial-mesenchymal transition, as suggested by altered ZO1 immunolabeling of RPE flatmounts. Our experiments indicate that RPE cells exposed to oxidative stress respond with a cytoprotective antioxidant and unfolded protein response, but develop mitochondrial impairment that contributed to epithelial mesenchymal transition. With similar responses in the RPE of early AMD samples, these results suggest that mitochondria are vulnerable to oxidative stress while the ER elicits a protective response during early AMD.
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| Overall design |
A total of 9 samples were analyzed: 3 control samples, 3 samples treated with 100ug/ml of Cigarette Smoke Condensate, and 3 samples treated with 250ug/ml of Cigarettes Smoke Condensate.
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| Contributor(s) |
Wang L, Barnett B, Ebrahimi K, Wan J, Qian J, Handa JT |
| Citation(s) |
24434119 |
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| Submission date |
Jul 22, 2013 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Marisol D Cano |
| E-mail(s) |
mcano1@jhmi.edu
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| Phone |
410 502 2939
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| Organization name |
Johns Hopkins University
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| Department |
Ophthalmology
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| Street address |
400 N Broadway
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21287 |
| Country |
USA |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| GSM1193884 |
RPE cells treated with vehicle control, rep1 |
| GSM1193885 |
RPE cells treated with vehicle control, rep2 |
| GSM1193886 |
RPE cells treated with vehicle control, rep3 |
| GSM1193887 |
RPE cells treated with 100 ug/ml of cigarette smoke condensate, rep1 |
| GSM1193888 |
RPE cells treated with 100 ug/ml of cigarette smoke condensate, rep2 |
| GSM1193889 |
RPE cells treated with 100 ug/ml of cigarette smoke condensate, rep3 |
| GSM1193890 |
RPE cells treated with 250 ug/ml of cigarette smoke condensate, rep1 |
| GSM1193891 |
RPE cells treated with 250 ug/ml of cigarette smoke condensate, rep2 |
| GSM1193892 |
RPE cells treated with 250 ug/ml of cigarette smoke condensate, rep3 |
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| Relations |
| BioProject |
PRJNA213007 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49107_RAW.tar |
195.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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