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ER Stress and Effects of DHA as an ER Stress Inhibitor

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Abstract

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.

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Acknowledgments

This work was supported in part by the National Institutes of Health Research grant R01NS048216 and R01NS48216 (DS) and the United States Department of Veterans Affairs VA RR&D#B6761R grant (CED).

Conflict of Interest

Gulnaz Begum declares that she has no conflict of interest.

Lloyd Harvey declares that he has no conflict of interest.

C. Edward Dixon declares that he has no conflict of interest.

Dandan Sun declares that she has no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Gulnaz Begum, Lloyd Harvey & Dandan Sun

  2. Department of Neurosurgery, Brain Trauma Research Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    C. Edward Dixon

  3. Department of Neurology, University of Pittsburgh Medical School, S-598 South Biomedical Science Tower (BST), 500 Terrace St, Pittsburgh, PA, 15213, USA

    Dandan Sun

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  1. Gulnaz Begum
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Correspondence to Dandan Sun.

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Gulnaz Begum and Lloyd Harvey contributed equally.

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Begum, G., Harvey, L., Dixon, C.E. et al. ER Stress and Effects of DHA as an ER Stress Inhibitor. Transl. Stroke Res. 4, 635–642 (2013). https://doi.org/10.1007/s12975-013-0282-1

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