scholarly journals Hepcidin overexpression in astrocytes alters brain iron metabolism and protects against amyloid-β induced brain damage in mice

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Xinwei Zhang ◽  
Yu-Jing Gou ◽  
Yating Zhang ◽  
Jie Li ◽  
Kang Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Metabolism ◽  
Cell Damage ◽  
Amyloid Β ◽  
Protective Role ◽  
Iron Level ◽  
Brain Iron ◽  
Brain Iron Metabolism ◽  
The Brain

Abstract Progressive iron accumulation in the brain and iron-induced oxidative stress are considered to be one of the initial causes of Alzheimer’s disease (AD), and modulation of brain iron level shows promise for its treatment. Hepcidin expressed by astrocytes has been speculated to regulate iron transport across the blood–brain barrier (BBB) and control the whole brain iron load. Whether increasing the expression of astrocyte hepcidin can reduce brain iron level and relieve AD symptoms has yet to be studied. Here, we overexpressed hepcidin in astrocytes of the mouse brain and challenged the mice with amyloid-β25–35 (Aβ25–35) by intracerebroventricular injection. Our results revealed that hepcidin overexpression in astrocytes significantly ameliorated Aβ25–35-induced cell damage in both the cerebral cortex and hippocampus. This protective role was also attested by behavioral tests of the mice. Our data further demonstrated that astrocyte-overexpressed hepcidin could decrease brain iron level, possibly by acting on ferroportin 1 (FPN1) on the brain microvascular endothelial cells (BMVECs), which in turn reduced Aβ25–35-induced oxidative stress and apoptosis, and ultimately protected cells from damage. This study provided in vivo evidences of the important role of astrocyte hepcidin in the regulation of brain iron metabolism and protection against Aβ-induced cortical and hippocampal damages and implied its potential in the treatment of oxidative stress-related brain disorders.

scholarly journals Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Subhankari Prasad Chakraborty ◽  
Panchanan Pramanik ◽  
Somenath Roy
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Cell Damage ◽  
Treated Group ◽  
Protective Role ◽  
Control Group ◽  
Similar Dose ◽  
Cellular Components

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

Quantitative imaging of intrinsic magnetic tissue properties using MRI signal phase: An approach to in vivo brain iron metabolism?

NeuroImage ◽  
2011 ◽  
Vol 54 (4) ◽  
pp. 2789-2807 ◽  
Author(s):  
Ferdinand Schweser ◽  
Andreas Deistung ◽  
Berengar Wendel Lehr ◽  
Jürgen Rainer Reichenbach
Keyword(s):  
Iron Metabolism ◽  
Quantitative Imaging ◽  
Brain Iron ◽  
Signal Phase ◽  
Tissue Properties ◽  
Brain Iron Metabolism

scholarly journals Alteration of Iron Concentration in Alzheimer’s Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4479
Author(s):  
Eleonora Ficiarà ◽  
Zunaira Munir ◽  
Silvia Boschi ◽  
Maria Eugenia Caligiuri ◽  
Caterina Guiot
Keyword(s):  
Iron Transport ◽  
Biological Fluids ◽  
Iron Status ◽  
Iron Concentration ◽  
Diagnostic Biomarker ◽  
Resonance Imaging ◽  
Brain Iron ◽  
Indirect Measurements ◽  
Brain Iron Metabolism ◽  
The Brain

Proper functioning of all organs, including the brain, requires iron. It is present in different forms in biological fluids, and alterations in its distribution can induce oxidative stress and neurodegeneration. However, the clinical parameters normally used for monitoring iron concentration in biological fluids (i.e., serum and cerebrospinal fluid) can hardly detect the quantity of circulating iron, while indirect measurements, e.g., magnetic resonance imaging, require further validation. This review summarizes the mechanisms involved in brain iron metabolism, homeostasis, and iron imbalance caused by alterations detectable by standard and non-standard indicators of iron status. These indicators for iron transport, storage, and metabolism can help to understand which biomarkers can better detect iron imbalances responsible for neurodegenerative diseases.

scholarly journals Apoferritin improves motor deficits in MPTP-treated mice through regulating brain iron metabolism and ferroptosis

iScience ◽  
2021 ◽  
pp. 102431
Author(s):  
Li-Mei Song ◽  
Zhi-Xin Xiao ◽  
Na Zhang ◽  
Xiao-Qi Yu ◽  
Wei Cui ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Motor Deficits ◽  
Brain Iron ◽  
Brain Iron Metabolism

Brain Iron Metabolism

2006 ◽  
Vol 13 (3) ◽  
pp. 142-148 ◽  
Author(s):  
Tracey A. Rouault ◽  
Sharon Cooperman
Keyword(s):  
Iron Metabolism ◽  
Brain Iron ◽  
Brain Iron Metabolism

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

scholarly journals Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Protein Levels ◽  
Key Factor ◽  
Protein Sulfhydryl ◽  
Mrna And Protein Expression ◽  
The Brain

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.

scholarly journals C60 Fullerene Prevents Restraint Stress-Induced Oxidative Disorders in Rat Tissues: Possible Involvement of the Nrf2/ARE-Antioxidant Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Olga O. Gonchar ◽  
Andriy V. Maznychenko ◽  
Nataliya V. Bulgakova ◽  
Inna V. Vereshchaka ◽  
Tomasz Tomiak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protein Expression ◽  
Restraint Stress ◽  
Stress Condition ◽  
Rat Tissues ◽  
Stress Exposure ◽  
The Brain ◽  
Nrf2 Protein

The effects of C60FAS (50 and 500 μg/kg) supplementation, in a normal physiological state and after restraint stress exposure, on prooxidant/antioxidant balance in rat tissues were explored and compared with the effects of the known exogenous antioxidant N-acetylcysteine. Oxidative stress biomarkers (ROS, O2⋅−, H2O2, and lipid peroxidation) and indices of antioxidant status (MnSOD, catalase, GPx, GST, γ-GCL, GR activities, and GSH level) were measured in the brain and the heart. In addition, protein expression of Nrf2 in the nuclear and cytosol fractions as well as the protein level of antiradical enzyme MnSOD and GSH-related enzymes γ-GCLC, GPx, and GSTP as downstream targets of Nrf2 was evaluated by western blot analysis. Under a stress condition, C60FAS attenuates ROS generation and O2⋅− and H2O2 releases and thus decreases lipid peroxidation as well as increases rat tissue antioxidant capacity. We have shown that C60FAS supplementation has dose-dependent and tissue-specific effects. C60FAS strengthened the antiradical defense through the upregulation of MnSOD in brain cells and maintained MnSOD protein content at the control level in the myocardium. Moreover, C60FAS enhanced the GSH level and the activity/protein expression of GSH-related enzymes. Correlation of these changes with Nrf2 protein content suggests that under stress exposure, along with other mechanisms, the Nrf2/ARE-antioxidant pathway may be involved in regulation of glutathione homeostasis. In our study, in an in vivo model, when C60FAS (50 and 500 μg/kg) was applied alone, no significant changes in Nrf2 protein expression as well as in activity/protein levels of MnSOD and GSH-related enzymes in both tissues types were observed. All these facts allow us to assume that in the in vivo model, C60FAS affects on the brain and heart endogenous antioxidative statuses only during the oxidative stress condition.

scholarly journals Vascular Dysfunction Induced by Mercury Exposure

2019 ◽  
Vol 20 (10) ◽  
pp. 2435 ◽  
Author(s):  
Tetsuya Takahashi ◽  
Takayoshi Shimohata
Keyword(s):  
Oxidative Stress ◽  
Vascular Dysfunction ◽  
Brain Parenchyma ◽  
Transport Systems ◽  
Mehg Exposure ◽  
In Vivo Models ◽  
The Central Nervous System ◽  
The Brain

Methylmercury (MeHg) causes severe damage to the central nervous system, and there is increasing evidence of the association between MeHg exposure and vascular dysfunction, hemorrhage, and edema in the brain, but not in other organs of patients with acute MeHg intoxication. These observations suggest that MeHg possibly causes blood–brain barrier (BBB) damage. MeHg penetrates the BBB into the brain parenchyma via active transport systems, mainly the l-type amino acid transporter 1, on endothelial cell membranes. Recently, exposure to mercury has significantly increased. Numerous reports suggest that long-term low-level MeHg exposure can impair endothelial function and increase the risks of cardiovascular disease. The most widely reported mechanism of MeHg toxicity is oxidative stress and related pathways, such as neuroinflammation. BBB dysfunction has been suggested by both in vitro and in vivo models of MeHg intoxication. Therapy targeted at both maintaining the BBB and suppressing oxidative stress may represent a promising therapeutic strategy for MeHg intoxication. This paper reviews studies on the relationship between MeHg exposure and vascular dysfunction, with a special emphasis on the BBB.

ChemInform Abstract: Brain Iron Metabolism and Its Perturbation in Neurological Diseases

ChemInform ◽  
2011 ◽  
Vol 42 (32) ◽  
pp. no-no ◽  
Author(s):  
Robert R. Crichton ◽  
David T. Dexter ◽  
Roberta J. Ward
Keyword(s):  
Iron Metabolism ◽  
Neurological Diseases ◽  
Brain Iron ◽  
Brain Iron Metabolism
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