Characterization of alpha1-antitrypsin as a heme oxygenase-1 suppressor in Alzheimer plasma.

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.

Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: implications for multiple sclerosis.

Proinflammatory cytokines, pathological iron deposition, and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). HO-1 mRNA levels and mitochondrial uptake of [(55)Fe]Cl(3)-derived iron were measured in rat astroglial cultures exposed to interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) alone or in combination with the heme oxygenase-1 (HO-1) inhibitors, tin mesoporphyrin (SnMP) or dexamthasone (DEX), or interferon beta1b (INF-beta). HO-1 expression in astrocytes was evaluated by immunohistochemical staining of spinal cord tissue derived from MS and control subjects.

Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene expression in oxidatively-challenged astroglia.

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that reduces superoxide anion to hydrogen peroxide in cell mitochondria. MnSOD is overexpressed in normal aging brain and in various central nervous system disorders; however, the mechanisms mediating the upregulation of MnSOD under these conditions remain poorly understood. We previously reported that cysteamine (CSH) and other pro-oxidants rapidly induce the heme oxygenase-1 (HO-1) gene in cultured rat astroglia followed by late upregulation of MnSOD in these cells.

Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD.

Background: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyzes the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillary tangles.

Methods: We investigated whether systemic HO-1 regulation is also deranged in AD patients and whether blood HO-1 measurements provide a peripheral biomarker of the disease.

Mitochondrial iron sequestration in dopamine-challenged astroglia: role of heme oxygenase-1 and the permeability transition pore.

Little is currently known concerning the mechanisms responsible for the excessive deposition of redox-active iron in the substantia nigra of subjects with Parkinson's disease (PD). In the present study, we demonstrate that dopamine promotes the selective sequestration of non-transferrin-derived iron by the mitochondrial compartment of cultured rat astroglia and that the mechanism underlying this novel dopamine effect is oxidative in nature. We also provide evidence that up-regulation of the stress protein heme oxygenase-1 (HO-1) is both necessary and sufficient for mitochondrial iron trapping in dopamine-challenged astroglia.