Date
2017Journal
Journal of Neuropathology and Experimental NeurologyPublisher
Oxford University PressType
Article
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α-Endosulfine (ARPP-19e) Expression in a Rat Model of StrokeAbstract
In nutrient restricted environments, the yeast endosulfines Igo1/2 are activated via TORC1 inhibition and function critically to initiate and coordinate the cellular stress response that promotes survival. We examined expression of αEnsa, the mammalian homolog of yeast endosulfines, in rat stroke. Prominent neuronal upregulation of αEnsa was identified in 3 patterns within the ischemic gradient: (1) neurons in GFAP−/HSF1+ cortex showed upregulation and near-complete nuclear translocation of αEnsa protein within hours of ischemic onset; (2) neurons in GFAP+/HSF1+ cortex showed upregulation in cytoplasm and nuclei that persisted for days; (3) neurons in GFAP+/HSF1− cortex showed delayed cytosolic-only upregulation that persisted for days. Findings were corroborated using in situ hybridization for ENSA mRNA. Rapamycin treatment was found to reduce infarct size and behavioral deficits and, in GFAP+/HSF1+ zones, enhance αEnsa neuronal nuclear translocation and mitigate cell death, relative to controls. Based on the conservation of TOR signaling across species, and on the finding that the Rim15-Igo1/2-PP2A module is triggered by substrate deprivation in eukaryotic yeast, we speculate that αEnsa is activated by substrate deprivation, functioning through the homologous MASTL-αEnsa/ARPP19-PP2A module to promote neuronal survival. In conjunction with recent studies suggesting a neuroprotective role, our data highlight a potential function for αEnsa within ischemic brain. Copyright 2017 American Association of Neuropathologists, Inc.Sponsors
This work was supported by grants to RIM from the Na-tional Institute of Neurological Disorders and Stroke (K08NS089830) and to JMS from the National Heart, Lung and Blood Institute (HL082517) and the National Institute of Neurological Disorders and Stroke (NS061808).Keyword
Alpha-endosulfineCerebral ischemia
ENSA
Molecular penumbra
Nutrient deprivation
Stroke
Sulfonylurea receptor 1 (SUR1)
αEnsa
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030619919&doi=10.1093%2fjnen%2fnlx074&partnerID=40&md5=6fa7374264b4aa26d8411939d40c9025; http://hdl.handle.net/10713/9967ae974a485f413a2113503eed53cd6c53
10.1093/jnen/nlx074
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