HEME, INFLAMMATION AND PARKINSON?S DISEASE
(Abstract release date: 05/21/15)
EHA Library. Gozzelino R. 06/12/15; 102997; PB1988
Disclosure(s): CHRONIC DISEASES RESEARCH CENTER (CEDOC)
Raffaella Gozzelino
Contributions
Contributions
Abstract
Abstract: PB1988
Type: Publication Only
Background
Heme is a metallo-compound, essential for the survival of most organisms. However, the ability of the central iron (Fe) atom, contained within its protoporphyrin ring, to participate in the Fenton chemistry and generate highly reactive hydroxyl radicals renders heme potentially toxic. Under inflammatory conditions, the release of heme from hemoproteins leads to unfettered oxidative stress, a deleterious effect allowing this molecule to sensitize parenchyma cells to undergo programmed cell death. We previously demonstrated that heme critically contributes to the pathogenesis of immune-mediated inflammatory diseases, by promoting the activation of the c-Jun N-terminal kinase signaling transduction pathway in response to pro-inflammatory agonists released in the course of the infection. The deleterious effect of heme is associated to tissue damage and disease severity, as upon hemolysis its release into circulation dictates the outcome of infectious diseases.
Aims
As infectious and inflammatory diseases are often associated to a certain degree of vascular leakage, it is possible that under these conditions the cytotoxicity of heme may affect also organs of restricted accessibility, such as the brain, thus increasing the risk and severity of neurodegenerative diseases.
Methods
This hypothesis has been investigated in mice by assessing whether the peripheral exogenous administration of heme or the release of heme upon exposure to immune-mediated inflammatory diseases enhances the severity of Parkinson’s disease.
Results
Preliminary data demonstrates that heme triggers neurodegeneration and enhances the susceptibility to Parkinson’s disease.
Summary
The protective effect of heme scavengers and proteins counteracting the pro-oxidant reactivity of Fe in preventing the development of Parkinson’s disease suggests that heme cytotoxicity may critically contribute to this disorder.
Keyword(s): Heme, Inflammation, Iron, Neural
Session topic: Publication Only
Type: Publication Only
Background
Heme is a metallo-compound, essential for the survival of most organisms. However, the ability of the central iron (Fe) atom, contained within its protoporphyrin ring, to participate in the Fenton chemistry and generate highly reactive hydroxyl radicals renders heme potentially toxic. Under inflammatory conditions, the release of heme from hemoproteins leads to unfettered oxidative stress, a deleterious effect allowing this molecule to sensitize parenchyma cells to undergo programmed cell death. We previously demonstrated that heme critically contributes to the pathogenesis of immune-mediated inflammatory diseases, by promoting the activation of the c-Jun N-terminal kinase signaling transduction pathway in response to pro-inflammatory agonists released in the course of the infection. The deleterious effect of heme is associated to tissue damage and disease severity, as upon hemolysis its release into circulation dictates the outcome of infectious diseases.
Aims
As infectious and inflammatory diseases are often associated to a certain degree of vascular leakage, it is possible that under these conditions the cytotoxicity of heme may affect also organs of restricted accessibility, such as the brain, thus increasing the risk and severity of neurodegenerative diseases.
Methods
This hypothesis has been investigated in mice by assessing whether the peripheral exogenous administration of heme or the release of heme upon exposure to immune-mediated inflammatory diseases enhances the severity of Parkinson’s disease.
Results
Preliminary data demonstrates that heme triggers neurodegeneration and enhances the susceptibility to Parkinson’s disease.
Summary
The protective effect of heme scavengers and proteins counteracting the pro-oxidant reactivity of Fe in preventing the development of Parkinson’s disease suggests that heme cytotoxicity may critically contribute to this disorder.
Keyword(s): Heme, Inflammation, Iron, Neural
Session topic: Publication Only
Abstract: PB1988
Type: Publication Only
Background
Heme is a metallo-compound, essential for the survival of most organisms. However, the ability of the central iron (Fe) atom, contained within its protoporphyrin ring, to participate in the Fenton chemistry and generate highly reactive hydroxyl radicals renders heme potentially toxic. Under inflammatory conditions, the release of heme from hemoproteins leads to unfettered oxidative stress, a deleterious effect allowing this molecule to sensitize parenchyma cells to undergo programmed cell death. We previously demonstrated that heme critically contributes to the pathogenesis of immune-mediated inflammatory diseases, by promoting the activation of the c-Jun N-terminal kinase signaling transduction pathway in response to pro-inflammatory agonists released in the course of the infection. The deleterious effect of heme is associated to tissue damage and disease severity, as upon hemolysis its release into circulation dictates the outcome of infectious diseases.
Aims
As infectious and inflammatory diseases are often associated to a certain degree of vascular leakage, it is possible that under these conditions the cytotoxicity of heme may affect also organs of restricted accessibility, such as the brain, thus increasing the risk and severity of neurodegenerative diseases.
Methods
This hypothesis has been investigated in mice by assessing whether the peripheral exogenous administration of heme or the release of heme upon exposure to immune-mediated inflammatory diseases enhances the severity of Parkinson’s disease.
Results
Preliminary data demonstrates that heme triggers neurodegeneration and enhances the susceptibility to Parkinson’s disease.
Summary
The protective effect of heme scavengers and proteins counteracting the pro-oxidant reactivity of Fe in preventing the development of Parkinson’s disease suggests that heme cytotoxicity may critically contribute to this disorder.
Keyword(s): Heme, Inflammation, Iron, Neural
Session topic: Publication Only
Type: Publication Only
Background
Heme is a metallo-compound, essential for the survival of most organisms. However, the ability of the central iron (Fe) atom, contained within its protoporphyrin ring, to participate in the Fenton chemistry and generate highly reactive hydroxyl radicals renders heme potentially toxic. Under inflammatory conditions, the release of heme from hemoproteins leads to unfettered oxidative stress, a deleterious effect allowing this molecule to sensitize parenchyma cells to undergo programmed cell death. We previously demonstrated that heme critically contributes to the pathogenesis of immune-mediated inflammatory diseases, by promoting the activation of the c-Jun N-terminal kinase signaling transduction pathway in response to pro-inflammatory agonists released in the course of the infection. The deleterious effect of heme is associated to tissue damage and disease severity, as upon hemolysis its release into circulation dictates the outcome of infectious diseases.
Aims
As infectious and inflammatory diseases are often associated to a certain degree of vascular leakage, it is possible that under these conditions the cytotoxicity of heme may affect also organs of restricted accessibility, such as the brain, thus increasing the risk and severity of neurodegenerative diseases.
Methods
This hypothesis has been investigated in mice by assessing whether the peripheral exogenous administration of heme or the release of heme upon exposure to immune-mediated inflammatory diseases enhances the severity of Parkinson’s disease.
Results
Preliminary data demonstrates that heme triggers neurodegeneration and enhances the susceptibility to Parkinson’s disease.
Summary
The protective effect of heme scavengers and proteins counteracting the pro-oxidant reactivity of Fe in preventing the development of Parkinson’s disease suggests that heme cytotoxicity may critically contribute to this disorder.
Keyword(s): Heme, Inflammation, Iron, Neural
Session topic: Publication Only
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