Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation.

ABSTRACT: Haem (ferrous protoporphyrin IX) is a reactive low-molecular-mass form of iron able to participate in oxygen-radical reactions that can lead to the degradation of proteins, lipids, carbohydrates and DNA. Oxygen-radical reactions are likely to occur upon tissue damage. Extracellular fluids rely on antioxidant mechanisms different from those found inside the cell, and circulating proteins limit radical reactions by converting pro-oxidant forms of iron into less-reactive forms. Of the compounds tested, only apohaemopexin and the chain-breaking antioxidant butylated hydroxytoluene inhibited (by more than 90%) haemin-stimulated peroxidation as measured by formation of conjugated dienes, thiobarbituric acid-reactive material from linolenic acid or peroxidation-induced phospholipid fluorescence. Haptoglobin, the haemoglobin-binding serum protein, was ineffective. Conversely, only haptoglobin significantly inhibited haemoglobin-stimulated lipid peroxidation. Iron-salt-induced lipid peroxidation was inhibited only by apotransferrin and the iron-chelator desferrioxamine. All lipid peroxidations were inhibited by the radical scavengers butylated hydroxytoluene and propyl gallate. These findings support the concept that transport and conservation of body iron stores are closely linked to antioxidant protection.

SUBMITTER: Gutteridge JM

PROVIDER: S-EPMC1135495 | biostudies-other | 1988 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Structural basis for haem piracy from host haemopexin by Haemophilus influenzae.

Project description:Haemophilus influenzae is an obligate human commensal/pathogen that requires haem for survival and can acquire it from several host haemoproteins, including haemopexin. The haem transport system from haem-haemopexin consists of HxuC, a haem receptor, and the two-partner-secretion system HxuB/HxuA. HxuA, which is exposed at the cell surface, is strictly required for haem acquisition from haemopexin. HxuA forms complexes with haem-haemopexin, leading to haem release and its capture by HxuC. The key question is how HxuA liberates haem from haemopexin. Here, we solve crystal structures of HxuA alone, and HxuA in complex with the N-terminal domain of haemopexin. A rational basis for the release of haem from haem-haemopexin is derived from both in vivo and in vitro studies. HxuA acts as a wedge that destabilizes the two-domains structure of haemopexin with a mobile loop on HxuA that favours haem ejection by redirecting key residues in the haem-binding pocket of haemopexin.

| S-EPMC4873976 | biostudies-literature

Intracellular distribution of haem after uptake by different receptors. Haem-haemopexin and haem-asialo-haemopexin.

Project description:How the interaction of haemopexin with two different receptors affects its subsequent metabolism and 'intracellular' haem transport was examined by using mesohaem-haemopexin and mesohaem-asialo-haemopexin. The physical properties of the two haem proteins, including their absorption and c.d. spectra, are similar. Binding studies in vitro showed that haem-asialo-haemopexin interacts with both the haemopexin-specific and galactose-specific receptors on liver plasma membranes, but that haem-haemopexin interacts only with the haemopexin receptor. In vivo haem-asialo-haemopexin rapidly interacts with the liver via the galactose-specific receptor, since the protein is extensively catabolized and uptake is blocked by asialofetuin. Haem iron from haem-asialo-haemopexin is not accumulated in the liver to the same extent as from intact haem-haemopexin, and the native sialylated protein is not proteolysed. Moreover, after fractionation of homogenized liver by using colloidal-silica gradients, liver-associated haem-haemopexin and haem-asialo-haemopexin produced distinctly different patterns for both protein and ligand, consistent with their uptake by two distinct receptors. These results demonstrate that the interaction of haemopexin with different receptors influences its subsequent metabolic fate and that haem iron from haem-haemopexin is efficiently conserved only if it enters the liver cell via the specific haemopexin receptor.

| S-EPMC1152800 | biostudies-other

GTP Cyclohydrolase I Confers Metabolic Protection Against Lipid Peroxidation in Glioblastoma

Project description:Guanosine triphosphate cyclohydrolase I (GCH1) was previously identified as a regulator of reactive oxygen species (ROS) in brain tumor initiating cells (BTICs). Elucidating the GCH1/Tetrahydrobiopterin (BH4) pathway in BTICs has unveiled the necessity for GCH1 to protect BTICs from lipid peroxidation. Within this study, we observed differences in lipid pathways and lipid metabolites during GCH1 modulation. Alteration to polyunsaturated fatty acids (PUFAs), a species of oxidatively vulnerable lipids, were altered during GCH1 knockdown. Pharmacological inhibition of BH4 with drugs known to cross the blood brain barrier (sulfasalazine and pyrimethamine) successfully reduced growth in GCH1 overexpressed BTICs, induced lipid peroxidation.

2024-12-01 | GSE251878 | GEO

Role of lipid peroxidation and PPAR-? in amplifying glucose-stimulated insulin secretion.

Project description:OBJECTIVE:Previous studies show that polyunsaturated fatty acids (PUFAs) increase the insulin secretory capacity of pancreatic ?-cells. We aimed at identifying PUFA-derived mediators and their cellular targets that are involved in the amplification of insulin release from ?-cells preexposed to high glucose levels. RESEARCH DESIGN AND METHODS:The content of fatty acids in phospholipids of INS-1E ?-cells was determined by lipidomics analysis. High-performance liquid chromatography was used to identify peroxidation products in ?-cell cultures. Static and dynamic glucose-stimulated insulin secretion (GSIS) assays were performed on isolated rat islets and/or INS-1E cells. The function of peroxisome proliferator-activated receptor-? (PPAR-?) in regulating insulin secretion was investigated using pharmacological agents and gene expression manipulations. RESULTS:High glucose activated cPLA(2) and, subsequently, the hydrolysis of arachidonic and linoleic acid (AA and LA, respectively) from phospholipids in INS-1E cells. Glucose also increased the level of reactive oxygen species, which promoted the peroxidation of these PUFAs to generate 4-hydroxy-2E-nonenal (4-HNE). The latter mimicked the GSIS-amplifying effect of high glucose preexposure and of the PPAR-? agonist GW501516 in INS-1E cells and isolated rat islets. These effects were blocked with GSK0660, a selective PPAR-? antagonist, and the antioxidant N-acetylcysteine or by silencing PPAR-? expression. High glucose, 4-HNE, and GW501516 also induced luciferase expression in a PPAR-?-mediated transactivation assay. Cytotoxic effects of 4-HNE were observed only above the physiologically effective concentration range. CONCLUSIONS:Elevated glucose levels augment the release of AA and LA from phospholipids and their peroxidation to 4-HNE in ?-cells. This molecule is an endogenous ligand for PPAR-?, which amplifies insulin secretion in ?-cells.

| S-EPMC3198069 | biostudies-literature

Aging decreases antioxidant effects and increases lipid peroxidation in the Apolipoprotein E deficient mouse.

Project description:In this study, to study the effect of aging and Apolipoprotein E (ApoE) deficiency on antioxidant ability in mice, we examined whether lipid peroxidation is promoted by aging in ApoE deficient (ApoE(-/-)) mice, which have a shorter lifespan than normal mice. The levels of thiobarbituric acid-reactive substances (TBARS), a biomarker of lipid peroxidation, were measured in plasma and liver in ApoE(-/-) mice aged 12 weeks (young) and 52 weeks (early stage of senescence). TBARS in plasma and liver were significantly increased by aging. Next, we examined the reasons why lipid peroxidation was promoted by aging, based on measurement of protein and mRNA levels for antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in liver in ApoE(-/-) mice aged 12 and 52 weeks. The levels of superoxide dismutase 1 and 2 in liver were significantly decreased by aging. The mRNA level of catalase was also significantly decreased and the mRNA levels of superoxide dismutase 1, superoxide dismutase 2 and glutathione peroxidase 1 all showed a tendency to decrease with age. These results suggest that lipid peroxidation is caused by reduction of antioxidant activity with aging and that this promotes senescence and shortens lifespan in ApoE(-/-) mice.

| S-EPMC3652298 | biostudies-literature

Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage

Project description:Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused be free Hb are found within the cardiovascular system and Hb triggered oxidative toxicity towards the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study we systematically investigated the structural, biochemical and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb’s oxidative reactions with lipoproteins providing dramatic protection against both pathways of toxicity. By these mechanisms Hp shifts Hb’s destructive pseudo-peroxidative reaction into a potential anti-oxidative function during peroxidative stress. HPAEC: A two color common reference design was chosen with 4-8 independent biological replicates of each condition. Each experimental sample (Cy5 labeled) was hybridized against a non-treated reference sample (Cy3 labeled). HUVEC: A two color common reference design was chosen with 3-4 independent biological replicates of each condition. Each experimental sample (Cy5 labeled) was hybridized against a non-treated reference sample (Cy3 labeled).

2015-04-30 | E-GEOD-46471 | biostudies-arrayexpress

Influence of cataract maturity on aqueous humor lipid peroxidation markers and antioxidant enzymes.

Project description:PURPOSE: The impact of cataract maturity on the aqueous humor (AH) oxidant/antioxidant balance is largely controversial. This study was aimed at assessing the relationships between cataract maturity and AH lipid peroxidation markers and enzymatic antioxidants. PATIENTS AND METHODS: The concentrations of conjugated dienes (CD), lipofuscin-like fluorescent end-products (LLF), soluble proteins, as well as the activities of superoxide dismutase (SOD) and catalase (CAT) were measured in AH samples from nondiabetic patients with either immature (n=15) or mature (n=15) cataract. RESULTS: In the overall AH sample, the mean values of CD, LLF, SOD, and CAT were 0.160 ± 0.024 (OD234), 166 ± 27 RFU, 24.5 ± 7.1 U/ml, and 31.9 ± 3.9 pmol/ml, respectively. CD was positively correlated with SOD (r=0.647; P<0.001), CAT (r=-0.394; P=0.031), and LLF (r=-0.399; P=0.029). The LLF was negatively correlated with SOD (r=-0.461; P=0.010). In samples adjusted for confounding factors, differences between immature and mature cataract groups regarding SOD, CD, LLF, and total proteins were significant (P<0.05; for all variables). The multiple logistic regression analysis identified LLF (OR=4.08; P=0.038) and SOD (OR=4.99; P=0.031) as independent predictors of cataract maturity. CONCLUSIONS: These results suggest that AH lipid peroxidation markers and antioxidants may significantly depend on the cataract maturity stage.

| S-EPMC3890749 | biostudies-other

GRP78 suppresses lipid peroxidation and promotes cellular antioxidant levels in glial cells following hydrogen peroxide exposure.

Project description:Oxidative stress, caused by the over production of reactive oxygen species (ROS), has been shown to contribute to cell damage associated with neurotrauma and neurodegenerative diseases. ROS mediates cell damage either through direct oxidation of lipids, proteins and DNA or by acting as signaling molecules to trigger cellular apoptotic pathways. The 78 kDa glucose-regulated protein (GRP78) is an ER chaperone that has been suggested to protect cells against ROS-induced damage. However, the protective mechanism of GRP78 remains unclear. In this study, we used C6 glioma cells transiently overexpressing GRP78 to investigate the protective effect of GRP78 against oxidative stress (hydrogen peroxide)-induced injury. Our results showed that the overexpression of GRP78 significantly protected cells from ROS-induced cell damage when compared to non-GRP78 overexpressing cells, which was most likely due to GRP78-overexpressing cells having higher levels of glutathione (GSH) andNad(p)hquinone oxidoreductase 1 (NQO1), two antioxidants that protect cells against oxidative stress. Although hydrogen peroxide treatment increased lipid peroxidation in non-GRP78 overexpressing cells, this increase was significantly reduced in GRP78-overexpressing cells. Overall, these results indicate that GRP78 plays an important role in protecting glial cells against oxidative stress via regulating the expression of GSH and NQO1.

| S-EPMC3901711 | biostudies-literature

Lipid peroxidation in cell death.

Project description:Disruption of redox homeostasis is a key phenotype of many pathological conditions. Though multiple oxidizing compounds such as hydrogen peroxide are widely recognized as mediators and inducers of oxidative stress, increasingly, attention is focused on the role of lipid hydroperoxides as critical mediators of death and disease. As the main component of cellular membranes, lipids have an indispensible role in maintaining the structural integrity of cells. Excessive oxidation of lipids alters the physical properties of cellular membranes and can cause covalent modification of proteins and nucleic acids. This review discusses the synthesis, toxicity, degradation, and detection of lipid peroxides in biological systems. Additionally, the role of lipid peroxidation is highlighted in cell death and disease, and strategies to control the accumulation of lipid peroxides are discussed.

| S-EPMC5319403 | biostudies-literature

Effect of Glutamine on Antioxidant Capacity and Lipid Peroxidation in the Breast Muscle of Heat-stressed Broilers via Antioxidant Genes and HSP70 Pathway.

Project description:This study investigated whether Glutamine (Gln) could be used as an additive to improve antioxidant capacity in the breast muscle of heat-stressed broilers. Two hundred and forty 22-day-old Arbor Acres broilers in the G1, G2, G3, and G4 groups (n = 60 each) were housed in a cyclic hot environment and fed the basal diet with 0%, 0.5%, 1.0%, and 1.5% Gln, respectively. Compared with the G1 group, dietary 1.5% Gln increased (p < 0.05) pH and b* values, but decreased (p < 0.05) L* cooking loss, drip loss, and water loss rate in breast meat of heat-stressed broilers. Malondialdehyde levels in the breast muscle were lower (p < 0.05) in 1.0% and 1.5% Gln groups than that of the heat-stress group. Compared with the G1 group, dietary 1.5% Gln increased (p < 0.05) catalase (CAT), glutathione, glutathione peroxidase (GSH-Px,) and total antioxidant capacity in the breast muscle of heat-stressed broilers. Furthermore, the CAT, GSH-Px, HSP70 mRNA expression levels, and HSP70 protein expression levels were increased (p < 0.05) in the G3 and G4 groups compared with the G1 group. In sum, Gln alleviated antioxidant capacity and lipid peroxidation in the breast muscle of heat-stressed broilers through antioxidant genes and HSP70 pathways.

| S-EPMC7143643 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data