Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western ...societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.
This study aimed to investigate how Akkermansia muciniphila can implicate type 2 diabetes mellitus and the mechanisms underlying the effects A. muciniphila on type 2 diabetes mellitus. Normal and ...streptozotocin-induced diabetic Sprague-Dawley rats were orally administered with A. muciniphila and solvent. After 4 weeks of treatment, diabetic rats orally administered with live or pasteurized A. muciniphila exhibited significant increase in the blood concentration of high-density lipoprotein, and decrease in the hepatic glycogen, serum plasminogen activator inhibitor-1, tumor necrosis factor-α, lipopolysaccharide, malondialdehyde and total glucagon-like peptide-1. Moreover, diabetic rats orally administered with A. muciniphila showed significantly increased species alpha diversity and gene function in gut microbes. These results indicated that A. muciniphila can improve liver function, reduce gluco/lipotoxicity, alleviate oxidative stress, suppress inflammation and normalize intestine microbiota of the host animal, thereby ameliorating type 2 diabetes mellitus. Akkermansia muciniphila might be considered as one of the ideal new probiotics used in the management of type 2 diabetes mellitus in future.
Lipid peroxidation involves a cascade of reactions in which production of free radicals occurs selectively in the lipid components of cellular membranes. Polyunsaturated fatty acids easily undergo ...lipid peroxidation chain reactions, which, in turn, lead to the formation of highly reactive electrophilic aldehydes. Among these, the most abundant aldehydes are 4-hydroxy-2-nonenal (HNE) and malondialdehyde, while acrolein is the most reactive. Proteins are susceptible to posttranslational modifications caused by aldehydes binding covalently to specific amino acid residues, in a process called Michael adduction, and these types of protein adducts, if not efficiently removed, may be, and generally are, dangerous for cellular homeostasis. In the present review, we focused the discussion on the selective proteins that are identified, by redox proteomics, as selective targets of HNE modification during the progression and pathogenesis of Alzheimer disease (AD). By comparing results obtained at different stages of the AD, it may be possible to identify key biochemical pathways involved and ideally identify therapeutic targets to prevent, delay, or treat AD.
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► The lipid peroxidation was increased throughout the progression of Alzheimer disease. ► The HNE modification of key proteins suggests that their involvement is critical in AD pathogenesis. ► Therapeutics to prevent lipid peroxidation may prevent or delay AD progression.
Of the many biological targets of oxidative stress, lipids are the most involved class of biomolecules. Lipid oxidation gives rise to a number of secondary products. Malondialdehyde (MDA) is the ...principal and most studied product of polyunsaturated fatty acid peroxidation. This aldehyde is a highly toxic molecule and should be considered as more than just a marker of lipid peroxidation. Its interaction with DNA and proteins has often been referred to as potentially mutagenic and atherogenic. This review is intended to briefly describe the physiological origin of MDA, to highlight its toxicity, describe and comment on the most recent methods of detection and discuss its occurrence and significance in pathology.
In vivo origin as well as reactivity and consequent toxicity of MDA are reviewed. The most recent and improved procedures for the evaluation of MDA in biological fluids are described and discussed. The evidence of the occurrence of increased MDA levels in pathology is described.
In the assessment of MDA, the most common methods of detection are insufficiently sensitive and disturbed by interference coming from related species or overestimation derived from stressing analysis conditions. Moreover, no recent nutritional or medical trials report the use of one of the new and more reliable methods, some of which are undoubtedly accessible to virtually all the laboratories provided with a common HPLC or a spectrofluorimeter.
We conducted a study to evaluate the interactive effect of NO and H2S on the cadmium (Cd) tolerance of wheat. Cadmium stress considerably reduced total dry weight, chlorophyll a and b content and ...ratio of Fv/Fm by 36.7, 48.6, 26.7 and 19.5%, respectively, but significantly enhanced the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA), endogenous H2S and NO, and the activities of antioxidant enzymes. Exogenously applied sodium nitroprusside (SNP) and sodium hydrosulfide (NaHS), donors of NO and H2S, respectively, enhanced total plant dry matter by 47.8 and 39.1%, chlorophyll a by 92.3 and 61.5%, chlorophyll b content by 29.1 and 27.2%, Fv/Fm ratio by 19.7 and 15.2%, respectively, and the activities of antioxidant enzymes, but lowered oxidative stress and proline content in Cd‐stressed wheat plants. NaHS and SNP also considerably limited both the uptake and translocation of Cd, thereby improving the levels of some key mineral nutrients in the plants. Enhanced levels of NO and H2S induced by NaHS were reversed by hypotuarine application, but they were substantially reduced almost to 50% by cPTIO (a NO scavenger) application. Hypotuarine was not effective, but cPTIO was highly effective in reducing the levels of NO and H2S produced by SNP in the roots of Cd‐stressed plants. The results showed that interactive effect of NO and H2S can considerably improve plant resistance against Cd toxicity by reducing oxidative stress and uptake of Cd in plants as well as by enhancing antioxidative defence system and uptake of some essential mineral nutrients.
Background and Objective
Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical ...factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis. Identification of such modified proteins in inflamed gingiva may explain, in part, how inflammation of the periodontal tissues may influence the development of rheumatoid arthritis.
Material and Methods
Gingival biopsies of healthy, mild and moderate periodontitis were triple stained with antibodies against malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins.
Results
Assessment of healthy gingival tissue revealed negligible staining for carbamylated, malondialdehyde‐acetaldehyde (MAA), or citrullinated proteins. Mild periodontitis was positive for all three modifications. Furthermore, there was an increase in staining intensity for carbamylated, citrullinated and MAA‐modified proteins in moderate periodontitis. Negative staining results were observed for the isotype controls.
Conclusion
This study provides evidence for the presence of citrullinated, carbamylated and MAA adduct modified proteins in inflamed periodontal tissues. The potential for these proteins to play a role in autoimmunity in a multi‐system inflammatory syndromic disease model now needs to be determined.
An excellent pre-column fluorescent derivatization reagent N-acetylhydrazine acridone for the quantitative determination of malondialdehyde was synthesized. Malondialdehyde was derivatized at 80 °C ...for 30 min in the presence of trichloroacetic acid. The separation of the derivative was performed on an Agilent ZORBAX SB-C18 column in conjunction with gradient elution. The excitation and emission wavelengths were 370 nm and 420 nm, respectively. The developed method demonstrated good linear relationship in the range of 0.02 pmol to 2.5 pmol (r = 0.9998). The calculated limit of detection and limit of quantification were 2.5 fmol and 8.3 fmol, respectively. The analytical precisions of the method were in the range of 1.36-2.27% (intra-day) and 2.36-3.92% (inter-day) respectively. The method was sensitive, specific and simple. It was successfully implemented to analysis the malondialdehyde in rat prostate.
This study evaluated the effects of varying levels of malondialdehyde (MDA) on the structural and foaming properties of the egg yolk proteins (EYPs), and the interaction between them was explored by ...molecular docking. The results showed that oxidative modification due to MDA increased the carbonyl content of EYPs by 4.49 times. Simultaneously, the total sulfhydryl content was reduced by 21.47%, and the solubility of EYPs was significantly decreased (p < 0.05). Continuous oxidation disorders the previously ordered structure of EYPs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that some proteins underwent crosslinking and aggregation with increased MDA oxidation, aligning with changes in particle size and zeta-potential. Moderate oxidation (<1 mmol/L) enhanced the foaming capacity and foam stability of EYPs. Additionally, molecular docking results uncovered favorable interactions between MDA and specific EYPs, primarily through hydrogen bonding. This research offers valuable insights into managing the functional and quality changes of yolk products during processing.
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•Malondialdehyde (MDA) changed the original conformation of egg yolk proteins (EYPs).•High levels of oxidation caused EYPs to form insoluble aggregates.•Moderate oxidation enhanced the foaming capacity and foam stability of EYPs.•MDA has non-covalent interactions with representative proteins of EYPs.
Antibodies to malondialdehyde (MDA)-modified macromolecules (adducts) have been detected in the serum of patients with atherosclerosis and correlate with the progression of this disease. However, the ...epitope and its formation have not been characterized. Studies have shown that excess MDA can be degraded to acetaldehyde, which combines with proteins to from a stable dihydropyridine adduct. To investigate, mice were immunized with MDA adducts in the absence of adjuvant and showed an increase in antibodies to MDA adducts and the carrier protein as the concentration of MDA was increased. In fact, a number of the commercially available antibodies to MDA-modified proteins were able to be inhibited by a chemical analogue, hexyl-MAA. Also, MDA–MAA adducts were detected in the serum and aortic tissue of JCR diabetic/atherosclerotic rats. These studies determined that commercially available antibodies to MDA predominantly react with the MAA adduct and are present in the JCR model of atherosclerosis in both the serum and the aortic tissue. Therefore, the immune response to MDA-modified proteins is most probably to the dihydropyridine structure (predominant epitope in MAA), which suggests that MAA adducts may play a role in the development and/or progression of atherosclerosis.
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