Increased Levels of 4-Hydroxynonenal Modified Proteins in Plasma of Children with Autoimmune Diseases

Grune, Tilman; Michel, Philip; Sitte, Nicolle; Eggert, W; Albrecht-Nebe, H; Esterbauer, Hermann; Siems, Werner

doi:10.1016/s0891-5849(96)00586-2

Cited by 93 publications

(68 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10 Thus, high levels of HNE have been detected in a large number of diseases. 11,12 Nevertheless, even if HNE can be detected by several methods, acquiring reliable values of HNE in vivo is considerably compromised by its rapid metabolism, its efflux and its steady-state concentration in specific tissues. 13 All cells are not equal regarding HNE detoxification.…”

Section: -Hydroxynonenal: a Highly Reactive Product Of Lipoperoxidationmentioning

confidence: 99%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

View full text Add to dashboard Cite

During the last three decades, 4-hydroxy-2-nonenal (HNE), a major a,b-unsaturated aldehyde product of n-6 fatty acid oxidation, has been shown to be involved in a great number of pathologies such as metabolic diseases, neurodegenerative diseases and cancers. These multiple pathologies can be explained by the fact that HNE is a potent modulator of numerous cell processes such as oxidative stress signaling, cell proliferation, transformation or cell death. The main objective of this review is to focus on the different aspects of HNE-induced cell death, with a particular emphasis on apoptosis. HNE is a special apoptotic inducer because of its abilities to form protein adducts and to propagate oxidative stress. It can stimulate intrinsic and extrinsic apoptotic pathways and interact with typical actors such as tumor protein 53, JNK, Fas or mitochondrial regulators. At the same time, due to its oxidant status, it can also induce some cellular defense mechanisms against oxidative stress, thus being involved in its own detoxification. These processes in turn limit the apoptotic potential of HNE. These dualities can imbalance cell fate, either toward cell death or toward survival, depending on the cell type, the metabolic state and the ability to detoxify.

show abstract

Section: -Hydroxynonenal: a Highly Reactive Product Of Lipoperoxidationmentioning

confidence: 99%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Such reactive oxidants can modify a variety of biological molecules, including polyunsaturated fatty acid-containing lipids generating lipid peroxides, which on decomposition lead to reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE). These lipid peroxidation-derived aldehydes (LPDAs) can bind covalently with a variety of amino acids of proteins to form MDAand HNE-modified protein adducts [7][8][9][10]. Increased lipid peroxidation [4,7,[11][12][13] and higher levels of MDA-and HNE-modified proteins are reported in patients with ADs [4,7,14,15].…”

Section: Introductionmentioning

confidence: 99%

Lipid peroxidation-derived aldehyde–protein adducts contribute to trichloroethene-mediated autoimmunity via activation of CD4+ T cells

Wang¹,

König²,

Ansari³

et al. 2008

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Lipid peroxidation is implicated in the pathogenesis of various autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind to proteins, but their role in eliciting an autoimmune response and contribution to disease pathogenesis remains unclear. To investigate the role of lipid peroxidation in the induction and/or exacerbation of autoimmune response, 6-week-old autoimmune-prone female MRL +/+ mice were treated for 4 weeks with trichloroethene (TCE; 10 mmol/kg, i.p., once a week), an environmental contaminant known to induce lipid peroxidation. Sera from TCE-treated mice showed significant levels of antibodies against MDA-and HNE-adducted proteins along with antinuclear antibodies. This suggested that TCE exposure not only caused increased lipid peroxidation, but also accelerated autoimmune responses. Furthermore, stimulation of cultured splenic lymphocytes from both control and TCE-treated mice with MDA-adducted mouse serum albumin (MDA-MSA) or HNE-MSA for 72 h showed significant proliferation of CD4 + T cells in TCE-treated mice as analyzed by flow cytometry. Also, splenic lymphocytes from TCE-treated mice released more IL-2 and IFN-γ into cultures when stimulated with MDA-MSA or HNE-MSA, suggesting a Th1 cell activation. Thus, our data suggest a role for lipid peroxidation-derived aldehydes in TCEmediated autoimmune responses and involvement of Th1 cell activation.

show abstract

“…Increased HNE formation has been detected in the brain of patients with Alzheimer disease (25), in the spinal cord following traumatic injury (33), in the plasma of children with autoimmune diseases (14), and in the lungs following ozone exposure (42). HNE exerts broad biological toxicity effects including inhibition of DNA and protein synthesis, modification of low-density lipoprotein, and modulation of gene expression (11).…”

mentioning

confidence: 99%

Modifications of proteins by 4-hydroxy-2-nonenal in the ventilatory muscles of rats

Hussain¹,

Matar²,

Barreiro³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Although 4-hydroxy-2-nonenal (HNE, a product of lipid peroxidation) is a major cause of oxidative damage inside skeletal muscles, the exact proteins modified by HNE are unknown. We used two-dimensional electrophoresis, immunoblotting, and mass spectrometry to identify selective proteins targeted by HNE inside the diaphragm of rats under two conditions: severe sepsis [induced by E. coli lipopolysaccharides (LPS)] and during strenuous muscle contractions elicited by severe inspiratory resistive loading (IRL). Diaphragm HNE-protein adduct formation (detected with a polyclonal antibody) increased significantly after 1 and 3 h of LPS injection with a return to baseline values thereafter. Similarly, HNE-protein adduct formation inside the diaphragm rose significantly after 6 but not 3 h of IRL. Mass spectrometry analysis of HNE-modified proteins revealed enolase 3b, aldolase and triosephosphate isomerase 1, creatine kinase, carbonic anyhdrase III, aconitase 2, dihydrolipoamide dehydrogenase, and electron transfer flavoprotein-β. Measurements of in vitro enolase activity in the presence of pure HNE revealed that HNE significantly attenuated enolase activity in a dose-dependent fashion, suggesting that HNE-derived modifications have inhibitory effects on enzyme activity. We conclude that lipid peroxidation products may inhibit muscle contractile performance through selective targeting of enzymes involved in glycolysis, energy production as well as CO2 hydration.

show abstract

Increased Levels of 4-Hydroxynonenal Modified Proteins in Plasma of Children with Autoimmune Diseases

Cited by 93 publications

References 21 publications

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Lipid peroxidation-derived aldehyde–protein adducts contribute to trichloroethene-mediated autoimmunity via activation of CD4+ T cells

Modifications of proteins by 4-hydroxy-2-nonenal in the ventilatory muscles of rats

Contact Info

Product

Resources

About