JournalJournal of Neuropathology and Experimental Neurology
PublisherOxford University Press
MetadataShow full item record
Other Titlesα-Endosulfine (ARPP-19e) Expression in a Rat Model of Stroke
AbstractIn 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.
SponsorsThis 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).
Sulfonylurea receptor 1 (SUR1)
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85030619919&doi=10.1093%2fjnen%2fnlx074&partnerID=40&md5=6fa7374264b4aa26d8411939d40c9025; http://hdl.handle.net/10713/9967
- Angiotensin II type 1 receptor blocker telmisartan reduces cerebral infarct volume and peri-infarct cytosolic phospholipase A(2) level in experimental stroke.
- Authors: Kobayashi T, Kawamata T, Shibata N, Okada Y, Kobayashi M, Hori T
- Issue date: 2009 Dec
- Rat mesangial alpha-endosulfine.
- Authors: Yee J, Cortes P, Barnes JL, Alviani R, Biederman JI, Szamosfalvi B
- Issue date: 2004 May
- Delayed progesterone treatment reduces brain infarction and improves functional outcomes after ischemic stroke: a time-window study in middle-aged rats.
- Authors: Yousuf S, Sayeed I, Atif F, Tang H, Wang J, Stein DG
- Issue date: 2014 Feb
- SB 234551 selective ET(A) receptor antagonism: perfusion/diffusion MRI used to define treatable stroke model, time to treatment and mechanism of protection.
- Authors: Legos JJ, Lenhard SC, Haimbach RE, Schaeffer TR, Bentley RG, McVey MJ, Chandra S, Irving EA, Andrew A Parsons, Barone FC
- Issue date: 2008 Jul
- RANTES has a potential to play a neuroprotective role in an autocrine/paracrine manner after ischemic stroke.
- Authors: Tokami H, Ago T, Sugimori H, Kuroda J, Awano H, Suzuki K, Kiyohara Y, Kamouchi M, Kitazono T, REBIOS Investigators.
- Issue date: 2013 Jun 23