Edinburgh Research Explorer

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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)673-683
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume33
Issue number5
DOIs
Publication statusPublished - May 2013

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.

    Research areas

  • Alzheimer’s , cell culture , energy metabolism, mitochondria, neurodegeneration, proteomics

Download statistics

No data available

ID: 6030864