Autophagy and Apoptosis Are Differentially Induced in Neurons and Astrocytes Treated with an In Vitro Mimic of the Ischemic Penumbra
| العنوان: | Autophagy and Apoptosis Are Differentially Induced in Neurons and Astrocytes Treated with an In Vitro Mimic of the Ischemic Penumbra |
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| المؤلفون: | Matthew E. Pamenter, Anelah K. McGinness, Guy Perkins, Xiang Q. Gu, Mark H. Ellisman, Gabriel G. Haddad |
| المصدر: | PLoS ONE PLoS ONE, Vol 7, Iss 12, p e51469 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cytoplasm, lcsh:Medicine, Apoptosis, Vacuole, Mitochondrion, Mitochondrial Dynamics, Brain Ischemia, Mice, Adenosine Triphosphate, 0302 clinical medicine, Molecular Cell Biology, Neurobiology of Disease and Regeneration, Annexin A5, lcsh:Science, Apoptotic Signaling Cascade, Cellular Stress Responses, Neurons, 0303 health sciences, Multidisciplinary, Cell Death, Penumbra, Cellular Structures, Signaling Cascades, Chromatin, Cell biology, Medicine, Apoptosis-inducing factor, Cellular Types, Research Article, Signal Transduction, Programmed cell death, Clinical Research Design, Nuclear Envelope, Poly ADP ribose polymerase, Biology, Signaling Pathways, Stress Signaling Cascade, 03 medical and health sciences, Autophagy, Animals, Animal Models of Disease, DNA Cleavage, 030304 developmental biology, Cell Nucleus, Staining and Labeling, lcsh:R, Subcellular Organelles, Astrocytes, Vacuoles, lcsh:Q, Molecular Neuroscience, 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | The development of clinical stroke therapies remains elusive. The neuroprotective efficacies of thousands of molecules and compounds have not yet been determined; however, screening large volumes of potential targets in vivo is severely rate limiting. High throughput screens (HTS) may be used to discover promising candidates, but this approach has been hindered by the lack of a simple in vitro model of the ischemic penumbra, a clinically relevant region of stroke-afflicted brain. Recently, our laboratory developed such a mimic (ischemic solution: IS) suitable for HTS, but the etiology of stress pathways activated by this model are poorly understood. The aim of the present study was to determine if the cell death phenotype induced by IS accurately mimics the in vivo penumbra and thus whether our model system is suitable for use in HTS. We treated cultured neuron and astrocyte cell lines with IS for up to 48 hrs and examined cellular energy state ([ATP]), cell and organelle morphology, and gene and molecular profiles related to stress pathways. We found that IS-treated cells exhibited a phenotype of mixed apoptosis/autophagy characteristic of the in vivo penumbra, including: (1) short-term elevation of [ATP] followed by progressive ATP depletion and Poly ADP Ribose Polymerase cleavage, (2) increased vacuole number in the cytoplasm, (3) mitochondrial rupture, decreased mitochondrial and cristae density, release of cytochrome C and apoptosis inducing factor, (4) chromatin condensation, nuclear lamin A and DNA cleavage, fragmentation of the nuclear envelope, and (5) altered expression of mRNA and proteins consistent with autophagy and apoptosis. We conclude that our in vitro model of the ischemic penumbra induces autophagy and apoptosis in cultured neuron and astrocyte cell lines and that this mimic solution is suitable for use in HTS to elucidate neuroprotective candidates against ischemic penumbral cell death. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e664ea6af687c6c21bed43b3f336f7aTest https://doi.org/10.1371/journal.pone.0051469Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9e664ea6af687c6c21bed43b3f336f7a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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