Adaptive changes in the neuronal proteome: mitochondrial energy production, endoplasmic reticulum stress, and ribosomal dysfunction in the cellular response to metabolic stress

Herrmann, A.G., Deighton, R.F., Le Bihan, T., McCulloch, M.C., Searcy, J.L., Kerr, L.E. and McCulloch, J. (2013) Adaptive changes in the neuronal proteome: mitochondrial energy production, endoplasmic reticulum stress, and ribosomal dysfunction in the cellular response to metabolic stress. Journal of Cerebral Blood Flow and Metabolism, 33(5), pp. 673-683. (doi: 10.1038/jcbfm.2012.204)

Abstract

Impaired energy metabolism in neurons is integral to a range of neurodegenerative diseases, from Alzheimer’s disease to stroke. To investigate the complex molecular changes underpinning cellular adaptation to metabolic stress, we have defined the proteomic response of the SH-SY5Y human neuroblastoma cell line after exposure to a metabolic challenge of oxygen glucose deprivation (OGD) in vitro. A total of 958 proteins across multiple subcellular compartments were detected and quantified by label-free liquid chromatography mass spectrometry. The levels of 130 proteins were significantly increased (P<0.01) after OGD and the levels of 63 proteins were significantly decreased (P<0.01) while expression of the majority of proteins (765) was not altered. Network analysis identified novel protein–protein interactomes involved with mitochondrial energy production, protein folding, and protein degradation, indicative of coherent and integrated proteomic responses to the metabolic challenge. Approximately one third (61) of the differentially expressed proteins was associated with the endoplasmic reticulum and mitochondria. Electron microscopic analysis of these subcellular structures showed morphologic changes consistent with the identified proteomic alterations. Our investigation of the global cellular response to a metabolic challenge clearly shows the considerable adaptive capacity of the proteome to a slowly evolving metabolic challenge.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McCulloch, Mrs Maj-Lis
• Authors: Herrmann, A.G., Deighton, R.F., Le Bihan, T., McCulloch, M.C., Searcy, J.L., Kerr, L.E., and McCulloch, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Cerebral Blood Flow and Metabolism
• Publisher: Nature Publishing Group
• ISSN: 0271-678X
• ISSN (Online): 1559-7016
• Copyright Holders: Copyright © 2013 ISCBFM
• First Published: First published in Journal of Cerebral Blood Flow and Metabolism 33(5):673-683
• Publisher Policy: Reproduced under a Creative Commons License