Edinburgh Research Explorer

Proteomic analysis of mitochondria in APOE transgenic mice and in response to an ischemic challenge

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

    Final published version, 745 KB, PDF document

    Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

http://www.nature.com/jcbfm/journal/v32/n1/full/jcbfm2011120a.html
Original languageEnglish
Pages (from-to)164-176
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 2012

Abstract

Apolipoprotein E (APOE)-ε4 is associated with a deleterious outcome after ischemic brain injury, which may involve abnormal regulation of mitochondrial function. We have assessed the mitochondrial proteomic response of APOE-ε3 and APOE-ε4 transgenic mice to transient global ischemic injury in the hippocampus. A genotype-dependent increase in ApoE levels in mitochondria was observed after ischemia, with APOE-ε4 mice showing significantly greater increases than APOE-ε3 mice. Quantitative analysis of the mitochondria-enriched fractions was performed using liquid-chromatography mass spectrometry coupled to label-free analysis. Of the 1,067 identified proteins, 274 were mitochondria associated. Mitochondrial protein expression was significantly different between genotypes under basal conditions as well as in response to global ischemia. A total of 12 mitochondrial proteins (including respiratory chain proteins NDUFA11, NDUFS3, NDUF5B, ATP5J, as well as ETFA, CYB5B, ATP6V1A, HSPA1B, OXR1, GLUL, IARS2, and PHYHIPL) were significantly altered with respect to genotype, global ischemia, or their interaction (P<0.01). A compelling interactome, created using proteins found to be significantly modulated by global ischemia (P<0.05), involved proteins that regulate energy production and oxidative stress. Thus, APOE genotype has a differential effect on the mitochondrial protein expression in the absence and presence of an injury, which may underlie the differing genotype susceptibility.

    Research areas

  • apolipoprotein E , ischemia, mitochondria , proteomics

Download statistics

No data available

ID: 2012806