Characterization of α1-antitrypsin as a heme oxygenase-1 suppressor in Alzheimer plasma
| Autor: | Howard Chertkow, Yogesh Mawal, Adrienne Liberman, Olivier C. Maes, Steven Kravitz, Demetrios J. Sahlas, Hyman M. Schipper, Khalil Mehindate, Haixiang Su, Dan Berlin, Calvin Melmed, Howard Bergman |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Aging DNA Complementary Hydrocortisone Iron Alpha (ethology) Fluorescent Antibody Technique Biology Neuropsychological Tests medicine.disease_cause Antioxidants Chromatography Affinity lcsh:RC321-571 Rats Sprague-Dawley chemistry.chemical_compound Cerebrospinal fluid Alzheimer Disease Internal medicine medicine Animals Humans RNA Messenger Genes Suppressor Heme lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Aged Microscopy Confocal Neurodegeneration Brain Middle Aged medicine.disease Blotting Northern Rats Heme oxygenase α1-Antitrypsin Endocrinology Neurology chemistry Heme oxygenase-1 alpha 1-Antitrypsin Immunology Choroid Plexus Alzheimer Choroid plexus Cognition Disorders Astrocyte Oxidative stress |
| Zdroj: | Neurobiology of Disease, Vol 24, Iss 1, Pp 89-100 (2006) |
| Popis: | Heme oxygenase-1 (HO-1) mRNA and protein levels are diminished in Alzheimer disease (AD) blood, cerebrospinal fluid (CSF) and choroid plexus. Herein, the presence of a heme oxygenase-1 suppressor (HOS) factor was ascertained by astroglial bioassay, biochemical techniques and immunofluorescence confocal microscopy. We report significantly augmented plasma HOS activity in AD patients relative to healthy elderly and neurological controls. The HOS factor was determined to be a 50-100 kDa heat-labile, heparin-binding glycoprotein that is unrelated to antioxidant ingestion, plasma total antioxidant capacity, circulating cortisol levels or apolipoprotein E epsilon4 carrier status. HOS bioactivity was recapitulated by exogenous alpha(1)-antitrypsin. alpha(1)-antitrypsin levels were significantly increased in AD plasma and correlated with HOS activity and MMSE scores. alpha(1)-antitrypsin immunodepletion attenuated HOS activity of AD plasma. In AD brain, alpha(1)-antitrypsin immunoreactivity was augmented and co-distributed with HO-1. HOS activity of alpha(1)-antitrypsin may curtail HO-1-dependent derangement of cerebral iron homeostasis and account for diminished HO-1 expression in AD peripheral tissues. |
| Databáze: | OpenAIRE |
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