| Title |
Urokinase plasminogen activator protects cardiac myocytes from oxidative damage and apoptosis via hOGG1 induction
|
|---|---|
| Published in |
Apoptosis, June 2017
|
| DOI | 10.1007/s10495-017-1388-9 |
| Pubmed ID | |
| Authors |
Philipp J. Hohensinner, Nikol Takacs, Christoph Kaun, Barbara Thaler, Konstantin A. Krychtiuk, Stefan Pfaffenberger, Arezu Aliabadi, Andreas Zuckermann, Kurt Huber, Johann Wojta |
| Abstract |
The role of uPA in tissue remodeling and cell migration is already well established. In addition, uPA was reported to stabilize p53, a key cell cycle control, DNA repair and apoptosis initiation protein. We aimed to determine the role of uPA-uPAR signaling towards cell survival or apoptosis in human adult cardiac myocytes (HACM). HACM were stimulated with uPA and DNA damage was inflicted by incubating cells with 200 µM H2O2. To analyze for apoptotic cells we applied TUNEL staining. Oxidative damage foci were analyzed by staining for 8-oxoguanine base pairs. In vivo qPCR analysis from RNA extracted from failing human hearts demonstrated a close relation of uPA with apoptosis and the p53 pathway. Furthermore, we observed a close correlation of uPA and p53 protein in homogenized tissue lysates. In vitro studies revealed that uPA preincubation protected HACM from oxidative damage induced cell death and reduced oxidative damage foci. uPA protection is independent of its catalytic activity, as the amino terminal fragment of uPA showed similar protection. A key enzyme for repairing oxidative DNA damage is the p53 target hOGG1. We found a significant increase of hOGG1 after pretreatment of HACM with uPA. Knockdown of hOGG1 completely abrogated the protective effect of uPA. We conclude that uPA might have a tissue protective role in human hearts besides its role in tissue remodeling. Tissue protection is mediated by the DNA repair protein hOGG1. This might be beneficial during tissue remodeling and thus could be a target for therapeutic approaches in the diseased heart. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 14 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 36% |
| Student > Bachelor | 3 | 21% |
| Researcher | 2 | 14% |
| Lecturer | 1 | 7% |
| Student > Master | 1 | 7% |
| Other | 1 | 7% |
| Unknown | 1 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 21% |
| Agricultural and Biological Sciences | 3 | 21% |
| Chemistry | 2 | 14% |
| Nursing and Health Professions | 1 | 7% |
| Environmental Science | 1 | 7% |
| Other | 2 | 14% |
| Unknown | 2 | 14% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 July 2017.
All research outputs
#20,431,953
of 22,985,065 outputs
Outputs from Apoptosis
#634
of 809 outputs
Outputs of similar age
#275,838
of 316,715 outputs
Outputs of similar age from Apoptosis
#8
of 12 outputs
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