STUDYID | STOREDB:STUDY1004 |
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CREATEDON | 2015-12-09 18:59:30 |
MODIFIEDON | 2020-11-10 11:33:28 |
UPLOADER | Zarko |
DOI | DOI:10.20348/STOREDB/1004 |
STUDY NAME | ||
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Does acetylation control the low-dose radiation response in endothelial cells? | ||
STUDY STATUS | ||
Published: Open access to everyone | ||
COUNTRY | ||
Germany | ||
PRINCIPAL INVESTIGATOR | ||
Dr Zarko Barjaktarovic | ||
BIOLOGICAL SAMPLE AVAILABLE | ||
No | ||
STUDY DESCRIPTION | ||
SummaryReversible lysine acetylation is a frequent posttranslational protein modification that regulates a broad array of signaling and metabolic pathways. We have shown previously that a radiation dose of 2 Gy causes immediate alterations in protein acetylation affecting signaling pathways such as p53, RhoA and Wnt in primary human cardiac microvascular endothelial cells. The goal of this study was to perform a systematic analysis of the endothelial cell response at very early (4 hours), early (24 hours) and late (7 days) time points after a moderate radiation dose of 0.5 Gy, with a focus on early changes in the acetylome followed by later alterations in the total proteome. Eighty-one proteins were found to be altered in their acetylation status, with mainly deacetylation taking place. Proteins involved in translation process, cytoskeletal organization, protein folding and chromatin structure were affected. The protein expression of sirtuin 1 and histone deacetyltransferases 3 and 6 was significantly increased, coinciding with the enhanced total deacetylase activity. The total proteome analysis indicated long-lasting changes in PI3K / Akt and RhoA signaling and ubiquitination. The acetylome and total proteome data were integrated using bioinformatics tools in order to find biological pathways that were persistently altered by irradiation and associated with early changes in the acetylome. This analysis suggested that irradiation induced alterations in RhoA signaling, cytoskeletal organization and eNOS signaling pathways. These changes were further validated by immunoblotting and enzymatic assays. This study shows for the first time that the interaction between acetylome and proteome plays a key role in the endothelial radiation response. The moderate dose of 0.5 Gy used here is relevant for the normal tissue side effects after radiation therapy. The study raises the question whether such adverse side effects could be avoided by altering the acetylation capacity of the tissue in question. |
DATASET NAME | ||
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Proteome_24h | ||
DOI | DOI:10.20348/STOREDB/1004/1006 |
Type: application/x-sqlite3
File size: 1 gigabytes
Uploaded on: 2020-11-10 10:59:57
DATASET NAME | ||
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Proteome_1week | ||
DOI | DOI:10.20348/STOREDB/1004/1005 |
Type: application/x-sqlite3
File size: 1 gigabytes
Uploaded on: 2020-11-10 11:33:04
Type: application/x-sqlite3
File size: 1 gigabytes
Uploaded on: 2020-11-10 11:32:16
Type: application/x-sqlite3
File size: 1 gigabytes
Uploaded on: 2020-11-10 11:17:05
Type: application/x-sqlite3
File size: 1 gigabytes
Uploaded on: 2020-11-10 11:16:54
DATASET NAME | ||
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Acetylome peptide protein data | ||
DOI | DOI:10.20348/STOREDB/1004/1004 |
Type: application/vnd.ms-excel
File size: 1 megabytes
Uploaded on: 2020-11-10 10:43:18