Autophagy and protein aggregation after brain ischemia

Authors

  • Chunli Liu,

    1. Neurochemistry Laboratory of Brain Injury, Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA
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  • Yanqin Gao,

    1. State Key Laboratory of Medical Neurobiology, Fudan University School of Medicine, Shanghai, China
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  • John Barrett,

    1. Neurochemistry Laboratory of Brain Injury, Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA
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  • Bingren Hu

    1. Neurochemistry Laboratory of Brain Injury, Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA
    2. State Key Laboratory of Medical Neurobiology, Fudan University School of Medicine, Shanghai, China
    3. Department of Anesthesiology & Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland, School of Medicine, Baltimore, Maryland, USA
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Address correspondence and reprint requests to Dr. Chunli Liu, Department of Neurology, University of Miami School of Medicine, PO Box 16960, Miami, FL 33136, USA. E-mail:bhu@med.Miami.edu

Abstract

J. Neurochem. (2010) 115, 68–78.

Abstract

Autophagy is the main degradation pathway responsible for eliminating abnormal protein aggregates and damaged organelles prevalent in neurons after transient cerebral ischemia. This study investigated whether accumulation of protein aggregate-associated organelles in post-ischemic neurons is a consequence of changes in autophagy. Electron microscopic analysis indicated that both autophagosomes and autolysosomes are significantly up-regulated in hippocampal CA1 and DG neurons after ischemia. The microtubule-associated protein light chain 3 (LC3)-II conjugate, a marker for autophagosomes assessed by western blotting, was up-regulated in post-ischemic brain tissues. Confocal microscopy showed that LC3 isoforms were located in living post-ischemic neurons. Treatment with chloriquine resulted in accumulation of LC3-II in sham-operated rats, but did not further change the LC3-II levels in post-ischemic brain tissues. The results indicate that at least part of the accumulation of protein aggregate-associated organelles seen following ischemia is likely to be because of failure of the autophagy pathway. The resulting protein aggregation on subcellular organelle membranes could lead to multiple organelle damage and to delayed neuronal death after transient cerebral ischemia.

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