Hypohaptoglobinemia associated with familial epilepsy.

Panter, S. Scott; Sadrzadeh, S.M. Hossein; Hallaway, Philip E.; Haines, J. L.; Anderson, Vernon E.; Eaton, John W.

doi:10.1084/jem.161.4.748

Cited by 87 publications

(45 citation statements)

References 28 publications

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“…However, intracortical injections of purified hemoglobin seem to interfere dramatically with brain physiology, as this promotes epileptic seizures (Rosen and Frumin, 1979). In agreement with this finding, reductions in plasma levels of haptoglobin are also associated with epileptic seizures (Panter et al, 1985).…”

Section: Introductionmentioning

confidence: 66%

On the Fate of Extracellular Hemoglobin and Heme in Brain

Lara

Kahn

Fonseca

et al. 2009

J Cereb Blood Flow Metab

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Intracerebral hemorrhage (ICH) is a major cause of disability in adults worldwide. The pathophysiology of this syndrome is complex, involving both inflammatory and redox components triggered by the extravasation of blood into the cerebral parenchyma. Hemoglobin, heme, and iron released therein seem be important in the brain damage observed in ICH. However, there is a lack of information concerning hemoglobin traffic and metabolism in brain cells. Here, we investigated the fate of hemoglobin and heme in cultured neurons and astrocytes, as well as in the cortex of adult rats. Hemoglobin was made traceable by conjugation to Alexa 488, whereas a fluorescent heme analogue (tin-protoporphyrin IX) was prepared to allow heme tracking. Using fluorescence microscopy we observed that neurons were more efficient in uptake hemoglobin and heme than astrocytes. Exposure of cortical neurons to hemoglobin or heme resulted in an oxidative stress condition. Viability assays showed that neurons were more susceptible to both hemoglobin and heme toxicity than astrocytes. Together, these results show that neurons, rather than astrocytes, preferentially take up hemoglobin-derived products, indicating that these cells are actively involved in the ICH-associated brain damage.

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Section: Introductionmentioning

confidence: 66%

On the Fate of Extracellular Hemoglobin and Heme in Brain

Lara

Kahn

Fonseca

et al. 2009

J Cereb Blood Flow Metab

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“…After CNS hemorrhage, some of this Hb enters the extracellular space due to erythrocyte lysis, which may be mediated by complement activation [1]. Although small quantities of free Hb may be removed by binding to its transport protein haptoglobin [2], deposition of iron in tissue surrounding experimental hematomas is consistent with local catabolism. A growing body of evidence suggests that free heme, iron and perhaps other Hb degradation products may contribute to oxidative injury after hemorrhagic insults [3].…”

Section: Introductionmentioning

confidence: 79%

Effect of heme oxygenase-1 on the vulnerability of astrocytes and neurons to hemoglobin

Chen-Roetling

Regan

2006

Biochemical and Biophysical Research Communications

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The heme oxygenase (HO) enzymes catalyze the rate-limiting step of heme breakdown. Prior studies have demonstrated that the vulnerability of neurons and astrocytes to hemoglobin is modified in cells lacking HO-2, the constitutive isoform. The present study assessed the effect of the inducible isoform, HO-1. Wild-type astrocytes treated for 3-5 days with 3-30 μM hemoglobin sustained no loss of viability, as quantified by LDH and MTT assays. The same treatment resulted in death of 25-50% of HO-1 knockout astrocytes, and a fourfold increase in protein oxidation. Cell injury was attenuated by transfer of the HO-1 gene, but not by bilirubin, the antioxidant heme breakdown product. Conversely, neuronal protein oxidation and cell death after hemoglobin exposure were similar in wild-type and HO-1 knockout cultures. These results suggest that HO-1 induction protects astrocytes from the oxidative toxicity of Hb, but has no effect on neuronal injury.

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“…Increased accumulation of iron in the brain and defective antioxidant defenses have been linked to both Parkinson and Alzheimer diseases (19 ). We previously showed that hypohaptoglobinemia was associated with high incidence and frequency of seizures in patients with idiopathic familial epilepsy (20 ). Defective haptoglobin-mediated clearance of free hemoglobin from the central nervous system could lead to hemoglobindependent central nervous system damage.…”

mentioning

confidence: 99%