Transglutaminase 2 protects against ischemic stroke
Autor: | Philip J. Dolan, Gail V.W. Johnson, Anthony J. Filiano, Janusz Tucholski, Gozde Colak |
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Rok vydání: | 2010 |
Předmět: |
Genetically modified mouse
Programmed cell death Tissue transglutaminase Blotting Western Ischemia Mice Transgenic Biology Article lcsh:RC321-571 Brain Ischemia Hypoxia inducible factor Mice Downregulation and upregulation GTP-Binding Proteins medicine Animals Protein Glutamine gamma Glutamyltransferase 2 Hypoxia lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Neurons Analysis of Variance Transglutaminases Reverse Transcriptase Polymerase Chain Reaction Wild type Brain Neuron medicine.disease Immunohistochemistry Magnetic Resonance Imaging Molecular biology Up-Regulation Stroke Transglutaminase 2 medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Neurology Hypoxia-inducible factors Cancer research biology.protein |
Zdroj: | Neurobiology of Disease, Vol 39, Iss 3, Pp 334-343 (2010) |
ISSN: | 0969-9961 |
Popis: | Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible factor (HIF) 1β and decreases the upregulation of hypoxic-induced proapoptotic genes. To investigate the role of TG2 in ischemic stroke in vivo, we used the murine, permanent middle cerebral artery (MCA) ligation model. TG2 mRNA levels are increased after MCA ligations, and transgenic mice that express human TG2 in neurons had significantly smaller infarct volumes than wild type littermates. Further, TG2 translocates into the nucleus within 2 hours post ligation. Nuclear-localized TG2 is also apparent in human stroke cases. TG2 suppressed the up regulation of the HIF-induced, proapoptotic gene, Noxa. The findings of this study indicate that TG2 plays a role in attenuating ischemic-induced cell death possibly by modulating hypoxic-induced transcriptional processes. |
Databáze: | OpenAIRE |
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