Journal
NEUROSCIENCE
Volume 146, Issue 2, Pages 562-572Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2007.01.050
Keywords
brain ischemia and reperfusion; protein aggregates; stress granules; TIA-1; translation arrest; ubiquitin
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Funding
- NIGMS NIH HHS [GM58905-8, R25 GM058905] Funding Source: Medline
- NINDS NIH HHS [NS044100, R01 NS044100, R01 NS044100-04] Funding Source: Medline
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The delayed and selective vulnerability of postischemic hippocampal cornu ammonis (CA) 1 pyramidal neurons correlates with a lack of recovery of normal protein synthesis. Recent evidence implicates sequestration of translational machinery into protein aggregates and stress granules as factors underlying persistent translation arrest in CA1 neurons. However, the relationship between protein aggregates and stress granules during brain reperfusion is unknown. Here we investigated the colocalization of protein aggregates and stress granules using immunofluorescence microscopy and pair-wise double labeling for ubiquitin/T cell internal antigen (TIA-1), ubiquitin/small ribosomal subunit protein 6 (S6), and TIA-1/S6. We evaluated the rat dorsal hippocampus at 1, 2 or 3 days of reperfusion following a 10 min global brain ischemic insult. At 1 day of reperfusion, ubiquitin-containing aggregates (ubi-protein clusters) occurred in neurons but did not colocalize with stress granules. At 2 days' reperfusion, only in CAI, cytoplasmic protein aggregates colocalized with stress granules, and ubiquitin-containing inclusions accumulated in the nuclei of CAI pyramidal neurons. Functionally, a convergence of stress granules and protein aggregates would be expected to sustain translation arrest and inhibit clearance of ubiquitinated proteins, both factors expected to contribute to CAI pyramidal neuron vulnerability. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
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