دورية أكاديمية
Unique properties of PTEN-L contribute to neuroprotection in response to ischemic-like stress.
| العنوان: | Unique properties of PTEN-L contribute to neuroprotection in response to ischemic-like stress. |
|---|---|
| المؤلفون: | Jochner, Magdalena C E, An, Junfeng, Lättig-Tünnemann, Gisela, Kirchner, Marieluise, Dagane, Alina, Dittmar, Gunnar, Dirnagl, Ulrich, Eickholt, Britta J, Harms, Christoph |
| المصدر: | Scientific reports 9(1), 3183 (2019). doi:10.1038/s41598-019-39438-1 |
| بيانات النشر: | Macmillan Publishers Limited, part of Springer Nature |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/600, Adaptor Proteins, Signal Transducing: genetics, Animals, Brain: metabolism, Brain: pathology, Brain Ischemia: genetics, Brain Ischemia: pathology, Cell Nucleus: genetics, Disease Models, Animal, GRB2 Adaptor Protein: genetics, Gene Expression Regulation: genetics, Glucose: metabolism, Humans, Mice, Neurons: metabolism, Neurons: pathology, Neuroprotection: genetics, Oxygen: metabolism, PTEN Phosphohydrolase: genetics, Protein Isoforms: genetics, Proteomics: methods, Signal Transduction: genetics, Stroke: genetics, Stroke: metabolism, Stroke: pathology |
| جغرافية الموضوع: | DE |
| الوصف: | Phosphatase and tensin homolog (PTEN) signalling might influence neuronal survival after brain ischemia. However, the influence of the less studied longer variant termed PTEN-L (or PTENα) has not been studied to date. Therefore, we examined the translational variant PTEN-L in the context of neuronal survival. We identified PTEN-L by proteomics in murine neuronal cultures and brain lysates and established a novel model to analyse PTEN or PTEN-L variants independently in vitro while avoiding overexpression. We found that PTEN-L, unlike PTEN, localises predominantly in the cytosol and translocates to the nucleus 10-20 minutes after glutamate stress. Genomic ablation of PTEN and PTEN-L increased neuronal susceptibility to oxygen-glucose deprivation. This effect was rescued by expression of either PTEN-L indicating that both PTEN isoforms might contribute to a neuroprotective response. However, in direct comparison, PTEN-L replaced neurons were protected against ischemic-like stress compared to neurons expressing PTEN. Neurons expressing strictly nuclear PTEN-L NLS showed increased vulnerability, indicating that nuclear PTEN-L alone is not sufficient in protecting against stress. We identified mutually exclusive binding partners of PTEN-L or PTEN in cytosolic or nuclear fractions, which were regulated after ischemic-like stress. GRB2-associated-binding protein 2, which is known to interact with phosphoinositol-3-kinase, was enriched specifically with PTEN-L in the cytosol in proximity to the plasma membrane and their interaction was lost after glutamate exposure. The present study revealed that PTEN and PTEN-L have distinct functions in response to stress and might be involved in different mechanisms of neuroprotection. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/pmid:30816308; info:eu-repo/semantics/altIdentifier/issn/2045-2322; https://pub.dzne.de/record/140527Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-06849%22Test |
| الإتاحة: | https://doi.org/10.1038/s41598-019-39438-1Test https://pub.dzne.de/record/140527Test https://pub.dzne.de/search?p=id:%22DZNE-2020-06849%22Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.55D99A78 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |