Selective Aryl Hydrocarbon Receptor Modulator 3,3′-Diindolylmethane Impairs AhR and ARNT Signaling and Protects Mouse Neuronal Cells Against Hypoxia
| العنوان: | Selective Aryl Hydrocarbon Receptor Modulator 3,3′-Diindolylmethane Impairs AhR and ARNT Signaling and Protects Mouse Neuronal Cells Against Hypoxia |
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| المؤلفون: | Agnieszka Wnuk, Joanna Rzemieniec, Wojciech Krzeptowski, Małgorzata Kajta, W. Lason, Ewa Litwa |
| المصدر: | Molecular Neurobiology. 53:5591-5606 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, 3,3'-Diindolylmethane, Indoles, genetic structures, Estrogen receptor, Apoptosis, Hippocampus, primary neuronal cell cultures, Mice, chemistry.chemical_compound, 0302 clinical medicine, RNA, Small Interfering, Cells, Cultured, Membrane Potential, Mitochondrial, Neurons, biology, Caspase 3, apoptosis, Cell Hypoxia, Neuroprotection, Cell biology, Neurology, neuroprotection, Microtubule-Associated Proteins, Signal Transduction, Aryl hydrocarbon receptor nuclear translocator, Cell Survival, Neuroscience (miscellaneous), Diindolylmethane, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cytochrome P-450 CYP1A1, medicine, Animals, Estrogen Receptor beta, Gene Silencing, RNA, Messenger, DIM, Cell damage, L-Lactate Dehydrogenase, Staining and Labeling, hypoxia, Aryl Hydrocarbon Receptor Nuclear Translocator, Aryl hydrocarbon receptor, medicine.disease, Enzyme Activation, 030104 developmental biology, Receptors, Aryl Hydrocarbon, chemistry, Immunology, biology.protein, sense organs, selective aryl hydrocarbon receptor modulators, Reactive Oxygen Species, 030217 neurology & neurosurgery |
| الوصف: | The neuroprotective potential of 3,3'-diindolylmethane (DIM), which is a selective aryl hydrocarbon receptor modulator, has recently been shown in cellular and animal models of Parkinson's disease and lipopolysaccharide-induced inflammation. However, there are no data concerning the protective capacity and mechanisms of DIM action in neuronal cells exposed to hypoxia. The aim of the present study was to investigate the neuroprotective potential of DIM against the hypoxia-induced damage in mouse hippocampal cells in primary cultures, with a particular focus on DIM interactions with the aryl hydrocarbon receptor (AhR), its nuclear translocator ARNT, and estrogen receptor β (ERβ). In the present study, 18 h of hypoxia induced apoptotic processes, in terms of the mitochondrial membrane potential, activation of caspase-3, and fragmentation of cell nuclei. These effects were accompanied by substantial lactate dehydrogenase release and neuronal cell death. The results of the present study demonstrated strong neuroprotective and anti-apoptotic actions of DIM in hippocampal cells exposed to hypoxia. In addition, DIM decreased the Ahr and Arnt mRNA expression and stimulated Erβ mRNA expression level. DIM-induced mRNA alterations were mirrored by changes in protein levels, except for ERβ, as detected by ELISA, Western blotting, and immunofluorescence labeling. We also demonstrated that DIM decreased the expression of AhR-regulated CYP1A1. Using specific siRNAs, we provided evidence that impairment of AhR and ARNT, but not ERβ plays a key role in the neuroprotective action of DIM against hypoxia-induced cell damage. This study may have implication for identifying new agents that could protect neurons against hypoxia by targeting AhR/ARNT signaling. |
| تدمد: | 1559-1182 0893-7648 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::630174ec8ddda07c0497730918f67e2fTest https://doi.org/10.1007/s12035-015-9471-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....630174ec8ddda07c0497730918f67e2f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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