naa a22 4500 51077587X CHVBK 20180411083230.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s12975-013-0282-1 doi (NATIONALLICENCE)springer-10.1007/s12975-013-0282-1 ER Stress and Effects of DHA as an ER Stress Inhibitor [Elektronische Daten] [Gulnaz Begum, Lloyd Harvey, C. Dixon, Dandan Sun] The endoplasmic reticulum (ER) functions in the synthesis, folding, modification, and transport of newly synthesized transmembrane and secretory proteins. The ER also has important roles in the storage of intracellular Ca2+ and regulation of Ca2+ homeostasis. The integrity of the Ca2+ homeostasis in the ER lumen is vital for proper folding of proteins. Dysregulation of ER Ca2+ could result in an increase in unfolded or misfolded proteins and ER stress. ER stress triggers activation of the unfolded protein response (UPR), which is a fundamentally adaptive cell response and functions as a cytoprotective mechanism by over-expression of relevant chaperones and the global shutdown of protein synthesis. UPR activation occurs when three key ER membrane-sensor proteins detect an accumulation of aberrant proteins. The UPR acts to alleviate ER stress, but if the stress is too severe or prolonged, apoptosis will be triggered. In this review, we focused on ER stress and the effects of docosahexaenoic acid (DHA) on ER stress. DHA and its bioactive compounds, such as protectins and resolvins, provide neuroprotection against oxidative stress and apoptosis and have the ability to resolve inflammation in neurological diseases. New studies reveal that DHA blocks inositol trisphosphate receptor (IP3R)-mediated ER Ca2+ depletion and ER stress. The administration of DHA post-traumatic brain injury (TBI) reduces ER stress, aberrant protein accumulation, and neurological deficits. Therefore, DHA presents therapeutic potentials for TBI via its pleiotropic effects including inhibition of ER stress. Springer Science+Business Media New York, 2013 C/EBP homologous protein nationallicence ER-associated protein degradation nationallicence ER Ca2+ dysregulation nationallicence Eukaryotic translation initiation factor 2α subunit nationallicence Unfolded protein response nationallicence Begum Gulnaz Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut Harvey Lloyd Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut Dixon C. Department of Neurosurgery, Brain Trauma Research Center, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut Sun Dandan Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut Translational Stroke Research Springer US; http://www.springer-ny.com 4/6(2013-12-01), 635-642 1868-4483 4:6<635 2013 4 12975 https://doi.org/10.1007/s12975-013-0282-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-013-0282-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Begum Gulnaz Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Harvey Lloyd Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Dixon C. Department of Neurosurgery, Brain Trauma Research Center, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Sun Dandan Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer US; http://www.springer-ny.com 4/6(2013-12-01), 635-642 1868-4483 4:6<635 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer