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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10499


    Title: Monitoring ER calcium and ER proteostasis under hypoxic conditions
    Authors: Trychta, KA;Yan, X;Anttila, J;Airavaara, M;Wu, KJ;Wang, Y;Henderson, MJ;Harvey, BK
    Contributors: Center for Neuropsychiatric Research
    Abstract: Under normal conditions, the calcium concentration in the lumen of the endoplasmic reticulum (ER) is 1,000 to 10,000 times higher than in the cytoplasm. ER calcium is important for many cellular functions, such as protein folding, lipid metabolism, and signaling pathways. Disruption of ER calcium homeostasis is implicated in multiple neurological diseases, including stroke. We used secreted ER calcium modulated proteins (SERCaMPs) to monitor ER calcium depletion in models of stroke. Using a previously described Gaussia luciferase (GLuc)-SERCaMP in vitro, we demonstrate here that oxygen-glucose deprivation increased ER calcium depletion and decreased cell viability. Additionally, we developed a series of GLuc-based SERCaMP reporters representing ~80 ER resident proteins and observed a widespread shift in the reporters following ischemia, which suggests changes to the ER proteome. This increase in SERCaMP response was attenuated by treatment with the ryanodine receptor (RyR) antagonist dantrolene, which also attenuated ER calcium depletion and increased cell viability. Rats injected with adeno-associated virus (AAV) vectors expressing GLucSERCaMP in the cortex showed evidence of ER calcium depletion following occlusion of the middle cerebral artery. Furthermore, dantrolene treatment reduced the infarct volume in rats. Collectively, our data support a model in which ischemic injury causes ER calcium depletion and the secretion of important ER resident proteins. These effects can be attenuated by stabilizing ER calcium and preventing loss of ER resident proteins.
    Date: 2017-04-04
    Relation: Cell Transplantation. 2017 Apr 4;26(4, Suppl.1):728-729.
    Link to: https://doi.org/10.3727/096368917X695146
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0963-6897&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000416626200076
    Appears in Collections:[王昀] 會議論文/會議摘要

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