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      Adaptive endoplasmic reticulum stress alters cellular responses to the extracellular milieu.

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          Abstract

          The ability to respond to perturbations in endoplasmic reticulum (ER) function is a critical property for all cells. In the presence of chronic ER stress, the cell must adapt so that cell survival is favored or the stress may promote apoptosis. In some pathological processes, such as neurodengeneration, persistent ER stress can be tolerated for an extended period, but eventually cell death occurs. It is not known how an adaptive response converts from survival into apoptosis. To gain a better understanding of the role of adaptive ER stress in neurodegeneration, in this study, with a neuronal cell line SH-SY5Y and primary motor neuron-glia cell mixed cultures, we induced adaptive ER stress and modified the extracellular environment with physiologically relevant changes that alone did not activate ER stress. Our data demonstrate that an adaptive ER stress favored neuronal cell survival, but when cells were exposed to additional physiological insults the level of ER stress was increased, followed by activation of the caspase pathway. Our results indicate that an adaptive ER stress response could be converted to apoptosis when the external cellular milieu changed, suggesting that the conversion from prosurvival to proapoptotic pathways can be driven by the external milieu. This conversion was due at least partially to an increased level of ER stress.

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          Author and article information

          Journal
          J. Neurosci. Res.
          Journal of neuroscience research
          1097-4547
          0360-4012
          May 2015
          : 93
          : 5
          Affiliations
          [1 ] Department of Neurosurgery, Pennsylvania State University, M.S. Hershey Medical Center, Hershey, Pennsylvania.
          Article
          10.1002/jnr.23541
          25581772
          9260460f-6fdc-4e92-b83c-5d4b4bdc1f16
          © 2015 Wiley Periodicals, Inc.
          History

          adaptive ER stress,neuronal death,physiological change

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