HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues
| Autor: | Adrienne Liberman, Carine Fillebeen, Wei Song, Hillel Zukor, Jean-Luc Guerquin-Kern, Ting-Di Wu, Hyman M. Schipper, Jeannie Mui, Hojatollah Vali, Kostas Pantopoulos |
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| Rok vydání: | 2009 |
| Předmět: |
Pathology
medicine.medical_specialty Time Factors Iron Ferroportin Spectrometry Mass Secondary Ion Transferrin receptor Electrophoretic Mobility Shift Assay Mitochondrion medicine.disease_cause Transfection Biochemistry Ferric Compounds Rats Sprague-Dawley Cellular and Molecular Neuroscience Microscopy Electron Transmission medicine Autophagy Animals Humans Inner mitochondrial membrane Cells Cultured chemistry.chemical_classification Cerebral Cortex biology Chemistry Cell biology Mitochondria Rats Ferritin medicine.anatomical_structure Animals Newborn Mesoporphyrins Transferrin Astrocytes biology.protein Neuroglia Oxidative stress Heme Oxygenase-1 Subcellular Fractions |
| Zdroj: | Journal of neurochemistry. 109(3) |
| ISSN: | 1471-4159 |
| Popis: | Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron. |
| Databáze: | OpenAIRE |
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