دورية أكاديمية
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, Guy A Perkins, Anelah K McGinness, Xiang Q Gu, Mark H Ellisman, Gabriel G Haddad |
المصدر: | PLoS ONE, Vol 7, Iss 12, p e51469 (2012) |
بيانات النشر: | Public Library of Science (PLoS), 2012. |
سنة النشر: | 2012 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 29869269 |
العلاقة: | http://europepmc.org/articles/PMC3520810?pdf=renderTest; https://doaj.org/toc/1932-6203Test |
DOI: | 10.1371/journal.pone.0051469 |
الوصول الحر: | https://doaj.org/article/f19cdce853e54a29869269dd9e06eabdTest |
رقم الانضمام: | edsdoj.f19cdce853e54a29869269dd9e06eabd |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 29869269 |
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DOI: | 10.1371/journal.pone.0051469 |