Hemin uptake and release by neurons and glia

Chen-Roetling, Jing; Cai, Ying; Lu, Xiangping; Regan, Raymond F.

doi:10.3109/10715762.2013.859386

Cited by 14 publications

(8 citation statements)

References 34 publications

(52 reference statements)

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“…While the actions of deferoxamine may involve chelation of iron and reduced free radical production, it may also prevent neuronal death by stabilizing hypoxia-inducible factor-1 α (HIF-1α) protein in neurons 33 . In addition, in cultured neurons, some of the protective effects of deferoxamine were mediated by enhancing release of hemin from neurons rather than an effect on hemin intake 34 . The present study that shows deferoxamine can also modulate brain CD163 levels.…”

Section: Discussionmentioning

confidence: 99%

CD163 Expression in Neurons After Experimental Intracerebral Hemorrhage

Liu

Cao

Hua

et al. 2017

Stroke

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Background and Purpose CD163, a receptor for hemoglobin, is involved in hemoglobin clearance following intracerebral hemorrhage (ICH). In contrast to microglial/macrophage CD163, neuronal CD163 hemoglobin has not been well studied. The current study examined the expression of neuronal CD163 in a pig model of ICH as well as in vitro rat cortical neurons, and the impact of deferoxamine on that expression. Methods There were 2 parts to this study. In the in vivo part, piglets had injection of autologous blood into the right frontal lobe. The time course of CD163 expression and the effect of deferoxamine on the expression of CD163 after ICH were determined in the grey matter. In the in vitro part, the levels of CD163 and neuronal death, and the effect of deferoxamine were examined in rat cortical neurons culture treated with hemoglobin. Results CD163 positive cells were found and the CD163 protein levels were upregulated in the ipsilateral grey matter after ICH. The CD163 levels peaked at days 1 and 3. The CD163 positive cells were co-located with NeuN, HO-2 and TUNEL positive cells. Deferoxamine treatment attenuated ICH-induced CD163 upregulation, and significantly reduced both brain CD163 and hemoglobin levels at day 3. Treating neuronal cultures with hemoglobin for 24 hours resulted in CD163 upregulation and increased cell death. Deferoxamine significantly attenuated the hemoglobin-induced neuronal death and CD163 upregulation. Conclusions CD163 is expressed in neurons and upregulated after ICH. Deferoxamine reduced ICH-induced CD163 upregulation and brain cell death in vivo, and hemoglobin-induced CD163 upregulation and neuronal death in vitro.

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Section: Discussionmentioning

confidence: 99%

CD163 Expression in Neurons After Experimental Intracerebral Hemorrhage

Liu

Cao

Hua

et al. 2017

Stroke

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“…Hb is the main component in blood, and Hb/heme/iron plays an indispensable role in the production of ROS and lipid ROS after ICH, which leads to secondary brain damage. After ICH, heme can incorporate into the plasma membrane and facilitate lipid peroxidation by increasing the sensitivity to the exogenous H 2 O 2 (Robinson et al, 2009 ; Chen-Roetling et al, 2014 ). ICH-induced ROS can lead to cell damage through lipid peroxidation, including apoptosis and another parallel pathway, maybe ferroptosis (Qu et al, 2016 ).…”

Section: The Underlying Mechanisms Of Neuronal Ferroptosis After Ichmentioning

confidence: 99%

Ferroptosis, a Regulated Neuronal Cell Death Type After Intracerebral Hemorrhage

Bai

Liu

Wang

2020

Front. Cell. Neurosci.

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Ferroptosis is a term that describes one form of regulated non-apoptotic cell death. It is triggered by the iron-dependent accumulation of lipid peroxides. Emerging evidence suggests a link between ferroptosis and the pathophysiological processes of neurological disorders, including stroke, degenerative diseases, neurotrauma, and cancer. Hemorrhagic stroke, also known as intracerebral hemorrhage (ICH), belongs to a devastating illness for its high level in morbidity and mortality. Currently, there are few established treatments and limited knowledge about the mechanisms of post-ICH neuronal death. The secondary brain damage after ICH is mainly attributed to oxidative stress and hemoglobin lysate, including iron, which leads to irreversible damage to neurons. Therefore, ferroptosis is becoming a common trend in research of neuronal death after ICH. Accumulative data suggest that the inhibition of ferroptosis may effectively prevent neuronal ferroptosis, thereby reducing secondary brain damage after ICH in animal models. Ferroptosis has a close relationship with oxidative damage and iron metabolism. This review reveals the pathological pathways and regulation mechanism of ferroptosis following ICH and then offers potential intervention strategies to mitigate neuron death and dysfunction after ICH.

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“…Iron–hemin uptake has been reported in neurons and astrocytes and is especially high in microglial cell cultures; neurons benefit from a high export of iron following the initial iron–hemin loading, and this export was exacerbated by treatment with DFO, a compound that attenuates hemin neurotoxicity (Chen-Roetling et al, 2014). As already mentioned, the brain produces the heme scavenger protein Hpx that protects from deleterious effects of heme.…”

Section: Brain Regulation Of Iron Metabolism During Strokementioning

confidence: 99%

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

DeGregorio-Rocasolano

2019

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In general, iron represents a double-edged sword in metabolism in most tissues, especially in the brain. Although the high metabolic demands of brain cells require iron as a redox-active metal for ATP-producing enzymes, the brain is highly vulnerable to the devastating consequences of excessive iron-induced oxidative stress and, as recently found, to ferroptosis as well. The blood–brain barrier (BBB) protects the brain from fluctuations in systemic iron. Under pathological conditions, especially in acute brain pathologies such as stroke, the BBB is disrupted, and iron pools from the blood gain sudden access to the brain parenchyma, which is crucial in mediating stroke-induced neurodegeneration. Each brain cell type reacts with changes in their expression of proteins involved in iron uptake, efflux, storage, and mobilization to preserve its internal iron homeostasis, with specific organelles such as mitochondria showing specialized responses. However, during ischemia, neurons are challenged with excess extracellular glutamate in the presence of high levels of extracellular iron; this causes glutamate receptor overactivation that boosts neuronal iron uptake and a subsequent overproduction of membrane peroxides. This glutamate-driven neuronal death can be attenuated by iron-chelating compounds or free radical scavenger molecules. Moreover, vascular wall rupture in hemorrhagic stroke results in the accumulation and lysis of iron-rich red blood cells at the brain parenchyma and the subsequent presence of hemoglobin and heme iron at the extracellular milieu, thereby contributing to iron-induced lipid peroxidation and cell death. This review summarizes recent progresses made in understanding the ferroptosis component underlying both ischemic and hemorrhagic stroke subtypes.

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Hemin uptake and release by neurons and glia

Cited by 14 publications

References 34 publications

CD163 Expression in Neurons After Experimental Intracerebral Hemorrhage

CD163 Expression in Neurons After Experimental Intracerebral Hemorrhage

Ferroptosis, a Regulated Neuronal Cell Death Type After Intracerebral Hemorrhage

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

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