scholarly journals Contribution of copper binding to the inhibition of lipid oxidation by plasmalogen phospholipids

1999 ◽  
Vol 340 (2) ◽  
pp. 377-383 ◽  
Author(s):  
Daniela HAHNEL ◽  
Thomas HUBER ◽  
Volker KURZE ◽  
Klaus BEYER ◽  
Bernd ENGELMANN
Keyword(s):  
Lipid Oxidation ◽  
Copper Ions ◽  
Aqueous Media ◽  
Oxidative Degradation ◽  
Direct Interaction ◽  
Molar Ratio ◽  
Protective Effects ◽  
Copper Binding ◽  
Enol Ether

The role of plasmalogen phospholipids for copper-induced lipid oxidation was evaluated. Using 1H-NMR we observed that the copper (CuSO4)-promoted oxidative degradation of polyunsaturated fatty acids in micellar solution was dose-dependently attenuated by the plasmalogen lysoplasmenylethanolamine from bovine brain (lysoBP-PtdEtn). This was due to a direct interaction of copper ions with the plasmalogen-specific enol ether double bond. The enol ether methine 1H signal decreased on the addition of copper, saturation being reached at a molar ratio of lysoBP-PtdEtn to copper of 1:1. The original 1H signal was recovered almost completely after the addition of EDTA. Enrichment of micelles and low-density lipoproteins (LDLs) with plasmalogen phospholipids led to a decrease in the Cu(II) concentration in the aqueous media. After loading of LDLs in vitro with BP-PtdEtn, the LDL-dependent formation of Cu(I) was decreased, in particular in particles experimentally supplemented with α-tocopherol. The suppression of copper-promoted lipid oxidation that was observed in the presence of plasmalogen phospholipids plus α-tocopherol was greater than the sum of the protective effects elicited by the two substances alone. In conclusion, the formation of a complex between copper ions and the plasmalogens accounts partly for their inhibition of copper-induced lipid oxidation.

scholarly journals Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD. Results HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes. Conclusion HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

Antioxidative properties of Sambacus nigra extracts

2015 ◽  
Vol 69 (9) ◽  
Author(s):  
Dominika Topoľská ◽  
Katarína Valachová ◽  
Peter Rapta ◽  
Stanislav Šilhár ◽  
Elena Panghyová ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Radical Scavenging ◽  
Oxidative Degradation ◽  
Protective Effects ◽  
Radical Scavenging Capacity ◽  
Scavenging Capacity ◽  
Diammonium Salt ◽  
Dose Dependent ◽  
Oxidative System

AbstractPotential protective effects of elderberry (Sambucus nigra) extracts against oxidative degradation of hyaluronan (HA) were detected in vitro. To induce free-radical-mediated HA degradation, Weissberger’s biogenic oxidative system, which mimics the situation of acute inflammation, was applied. Time- and dose-dependent changes of dynamic viscosity of the HA solutions in the presence and absence of two elderberry extracts produced in 2006 and 2012 were recorded by rotational viscometry (RV). Radical scavenging capacity of both extracts was investigated by the spectrocolorimetric ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt] assay and the “inverted” ABTS assay. Oxygen consumption of the system oxidizing HA either in the absence or presence of the elderberry extracts was determined. The results of RV revealed that an addition of the newer extract (2012) promoted the inhibition of HA degradation more markedly compared to the older extract (2006). The same effect of both extracts on ABTS

scholarly journals A Novel Pentapeptide Inhibitor Reduces Amyloid Deposit Formation by Direct Interaction with hIAPP

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yue Shi ◽  
Wu Lv ◽  
Ao Jiao ◽  
Chengshuo Zhang ◽  
Jialin Zhang
Keyword(s):  
Self Assembly ◽  
Direct Interaction ◽  
Binding Mode ◽  
Amyloid Deposit ◽  
Molar Ratio ◽  
Amyloid Aggregation ◽  
Islet Amyloid ◽  
Deposit Formation ◽  
Amyloid Deposits

Backgrounds. The presence of amyloid deposits of human islet amyloid polypeptide (hIAPP) in islet β-cells has been associated with type 2 diabetes occurrence and islet graft failure. Self-assembly into oligomers and fibrils during the process of aggregation by hIAPP can lead to failure and depletion of β-cells. Studies have shown that some critical regions of hIAPP might contribute to the aggregation. Thus, many studies focused on finding the effective molecules, especially the short-peptide inhibitors, that bind to these regions and disrupt the aggregation of hIAPP. In the present study, a novel pentapeptide inhibitor Phe-Leu-Pro-Asn-Phe (FLPNF) was designed and its effectiveness on the inhibition of the formation of amyloid deposits was examined. Methods. The binding mode between FLPNF and hIAPP was performed using molecular docking. The effectiveness of FLPNF on inhibiting hIAPP amyloid aggregation was tested by Thioflavin T (ThT) staining. Furthermore, negative stain electron microscopy was used to observe hIAPP fibrils. A biolayer interferometry analysis was used to identify the interaction between FLPNF and hIAPP. In addition, the cytotoxicity toward INS-1 cells was tested by a cell proliferation assay. Results. FLPNF was predicted to have a compact conformation to bind at the site of hIAPP. FLPNF strongly inhibited the amyloid aggregation of hIAPP at a 10 : 1 molar ratio in vitro. Coincubation of FLPNF with hIAPP decreased the amount of hIAPP fibrils. Furthermore, a direct interaction between FLPNF and hIAPP was confirmed. FLPNF could also decrease the cytotoxic effect of hIAPP. Conclusions. The novel pentapeptide inhibitor FLPNF was constructed and inhibited the aggregation through direct binding to hIAPP. It is considered a suitable inhibitor for hIAPP amyloid deposit formation.

scholarly journals Anti-apoptotic protein Bcl-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)

2004 ◽  
Vol 383 (2) ◽  
pp. 361-370 ◽  
Author(s):  
Elena S. DREMINA ◽  
Victor S. SHAROV ◽  
Keshava KUMAR ◽  
Asma ZAIDI ◽  
Elias K. MICHAELIS ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Sarcoplasmic Reticulum ◽  
Conformational Transition ◽  
Direct Interaction ◽  
Molar Ratio ◽  
Endoplasmic Reticulum Calcium ◽  
Oxidative Inactivation ◽  
Complete Inactivation

The anti-apoptotic effect of Bcl-2 is well established, but the detailed mechanisms are unknown. In the present study, we show in vitro a direct interaction of Bcl-2 with the rat skeletal muscle SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), leading to destabilization and inactivation of the protein. Recombinant human Bcl-2Δ21, a truncated form of Bcl-2 with a deletion of 21 residues at the C-terminal membrane-anchoring region, was expressed and affinity-purified as a glutathione S-transferase fusion protein. Bcl-2Δ21 co-immunoprecipitated and specifically interacted with SERCA in an in vitro-binding assay. The original level of Bcl-2 in sarcoplasmic reticulum vesicles was very low, i.e. hardly detectable by immunoblotting with specific antibodies. The addition of Bcl-2Δ21 to the sarcoplasmic reticulum resulted in the inhibition of the Ca2+-ATPase activity dependent on the Bcl-2Δ21/SERCA molar ratio and incubation time. A complete inactivation of SERCA was observed after 2.5 h of incubation at approx. 2:1 molar ratio of Bcl-2Δ21 to SERCA. In contrast, Bcl-2Δ21 did not significantly change the activity of the plasma-membrane Ca2+-ATPase. The redox state of the single Cys158 residue in Bcl-2Δ21 and the presence of GSH did not affect SERCA inhibition. The interaction of Bcl-2Δ21 with SERCA resulted in a conformational transition of SERCA, assessed through a Bcl-2-dependent increase in SERCA thiols available for the labelling with a fluorescent reagent. This partial unfolding of SERCA did not lead to a higher sensitivity of SERCA towards oxidative inactivation. Our results suggest that the direct interaction of Bcl-2 with SERCA may be involved in the regulation of apoptotic processes in vivo through modulation of cytoplasmic and/or endoplasmic reticulum calcium levels required for the execution of apoptosis.

scholarly journals Elucidation of Interaction between Whey Proteins and Proanthocyanidins and Its Protective Effects on Proanthocyanidins during In-Vitro Digestion and Storage

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5468
Author(s):  
Chenyu Tang ◽  
Bing Tan ◽  
Xiangjun Sun
Keyword(s):  
Hydrophobic Interactions ◽  
Retention Rate ◽  
Whey Proteins ◽  
In Vitro Digestion ◽  
Molar Ratio ◽  
Protective Effects ◽  
Food Ingredients ◽  
Oligomeric Proanthocyanidins ◽  
And Storage

Whey proteins and oligomeric proanthocyanidins have nutritional value and are widely used in combination as food supplements. However, the effect of the interactions between proanthocyanidins and whey proteins on their stability has not been studied in depth. In this work, we aimed to characterize the interactions between β-Lactoglobulin (β-LG) and α-lactalbumin (α-LA) and oligomeric proanthocyanidins, including A1, A2, B1, B2, B3, and C1, using multi-spectroscopic and molecular docking methods. Fluorescence spectroscopic data revealed that all of the oligomeric proanthocyanidins quenched the intrinsic fluorescence of β-LG or α-LA by binding-related fluorescence quenching. Among the six oligomeric proanthocyanidins, A1 showed the strongest affinity for β-LG (Ka = 2.951 (±0.447) × 104 L∙mol−1) and α-LA (Ka = 1.472 (±0.236) × 105 L∙mol−1) at 297 K. β-LG/α-LA and proanthocyanidins can spontaneously form complexes, which are mainly induced by hydrophobic interactions, hydrogen bonds, and van der Waals forces. Fourier-transform infrared spectroscopy (FTIR) and circular dichroism spectroscopy showed that the secondary structures of the proteins were rearranged after binding to oligomeric proanthocyanidins. During in vitro gastrointestinal digestion, the recovery rate of A1 and A2 increased with the addition of WPI by 11.90% and 38.43%, respectively. The addition of WPI (molar ratio of 1:1) increased the retention rate of proanthocyanidins A1, A2, B1, B2, B3, and C1 during storage at room temperature by 14.01%, 23.14%, 30.09%, 62.67%, 47.92%, and 60.56%, respectively. These results are helpful for the promotion of protein–proanthocyanidin complexes as functional food ingredients in the food industry.

scholarly journals Bioaccumulation of Copper Ions by Escherichia coli Expressing Vanabin Genes from the Vanadium-Rich Ascidian Ascidia sydneiensis samea

2003 ◽  
Vol 69 (11) ◽  
pp. 6442-6446 ◽  
Author(s):  
Tatsuya Ueki ◽  
Yasuhisa Sakamoto ◽  
Nobuo Yamaguchi ◽  
Hitoshi Michibata
Keyword(s):  
Escherichia Coli ◽  
Metal Binding ◽  
Binding Proteins ◽  
Copper Ions ◽  
Maltose Binding Protein ◽  
Molar Ratio ◽  
Periplasmic Space ◽  
E Coli ◽  
Genes Encoding

ABSTRACT The genes encoding two vanadium-binding proteins, vanabin1 and vanabin2, from a vanadium-rich ascidian, Ascidia sydneiensis samea, were recently identified and cloned (T. Ueki, T. Adachi, S. Kawano, M. Aoshima, N. Yamaguchi, K. Kanamori, and H. Michibata, Biochim. Biophys. Acta 1626:43-50, 2003). The vanabins were found to bind vanadium(IV), and an excess of copper(II) ions inhibited the binding of vanadium(IV) to the vanabins in vitro. In this study, we constructed Escherichia coli strains that expressed vanabin1 or vanabin2 fused to maltose-binding protein (MBP) in the periplasmic space. We found that both strains accumulated about twenty times more copper(II) ions than the control BL21 strain, while no significant accumulation of vanadium was observed. The strains expressing either MBP-vanabin1 or MBP-vanabin2 absorbed approximately 70% of the copper ions in the medium to which 10 μM copper (II) ions were initially added. The MBP-vanabin1 and MBP-vanabin2 protein expressed in the periplasm bound to copper ions at a copper:protein molar ratio of 8:1 and 5:1, respectively, but MBP did not bind to copper ions. These data showed that the metal-binding proteins vanabin1 and vanabin2 bound copper ions directly and enhanced the bioaccumulation of copper ions by E. coli.

scholarly journals Membrane composition can influence the rate of Al3+-mediated lipid oxidation: effect of galactolipids

1998 ◽  
Vol 333 (3) ◽  
pp. 833-838 ◽  
Author(s):  
Sandra V. VERSTRAETEN ◽  
Carl L. KEEN ◽  
Mari S. GOLUB ◽  
Patricia I. OTEIZA
Keyword(s):  
Phase Separation ◽  
Physical Properties ◽  
Lipid Oxidation ◽  
Molar Ratio ◽  
Membrane Composition ◽  
Postnatal Exposure ◽  
Stimulatory Action ◽  
Myelin Lipid ◽  
Oxidation Rates

In the first part of the present study we investigated the effects of pre-natal and early postnatal exposure of mice to high levels of dietary Al3+ on myelin lipid composition and lipid oxidation. We found: (1) a significantly higher (104%; P< 0.01) content of brain myelin galactolipids in the high-Al3+ group than in controls, and, (2) a significant correlation (r2 = 0.70; P< 0.01) between the concentration of myelin galactolipids and TBARS (2-thiobarbituric acid-reactive substances) content, a parameter of lipid oxidation. Based on these results, we evaluated in an in vitro model (liposomes) whether galactolipids could affect the capacity of Al3+ to stimulate Fe2+-initiated lipid oxidation, and whether this effect could be due to the promotion of changes in membrane physical properties (membrane phase separation and rigidification). The presence of galactolipids (10–40 mol%) in the liposomes caused a concentration-dependent increase in the stimulatory effect of Al3+ on Fe2+-induced TBARS production, and on the ability of Al3+ to induce phase separation and membrane rigidification. The capacity of Al3+ (10–100 µM) to induce lateral phase separation in liposomes composed of phosphatidylcholine/phosphatidylserine/galactolipid (36:24:40, molar ratio) was correlated significantly (r2 = 0.99; P< 0.001) with the stimulatory action of Al3+ on Fe2+-induced TBARS production. We propose that the high content of galactolipids found in myelin from Al3+-intoxicated mice could favour Al3+-induced changes in membrane physical properties, with the subsequent acceleration of lipid oxidation rates.

scholarly journals Delayed oxidative degradation of polyunsaturated diacyl phospholipids in the presence of plasmalogen phospholipids in vitro

1997 ◽  
Vol 323 (3) ◽  
pp. 807-814 ◽  
Author(s):  
Daniela REISS ◽  
Klaus BEYER ◽  
Bernd ENGELMANN
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Oxidative Degradation ◽  
Methine Proton ◽  
Peroxyl Radicals ◽  
Double Bonds ◽  
Enol Ether ◽  
Chemical Determination ◽  
Triton X

The oxidative degradation of plasmalogen (alkenylacyl) phospholipids was analysed in the absence and the presence of polyunsaturated ester phospholipids by 1H-NMR and by chemical determination. Brain lysoplasmenylethanolamine (lyso-P-PE), brain P-PE and erythrocyte P-PE, containing an increasing number of intrachain double bonds at sn2, were oxidized with 2,2´-azobis-(2-amidinopropane hydrochloride) (AAPH; 2 or 10 mM) in Triton X-100 micelles (detergent/phospholipid 1:5, mol/mol). The formation of two peroxyl radicals was accompanied by the degradation of approx. one molecule of brain lyso-P-PE. On oxidation of brain P-PE or erythrocyte P-PE (320 nmol) with 2 mM AAPH, the (α-vinyl) methine 1H signal of the enol ether decreased more rapidly than the methine proton peak of intrachain double bonds. The rate of enol ether degradation increased in the order: erythrocyte P-PE > brain P-PE > brain lyso-P-PE. The disappearance of the polyunsaturated ester phospholipids 1-palmitoyl-2-arachidonoyl phosphatidylcholine (16:0/20:4-PC) and 1-palmitoyl-2-linoleoyl phosphatidylcholine (16:0/18:2-PC) (100 nmol), as induced by 10 mM AAPH, was nearly completely inhibited by the plasmalogens (25 nmol) in the first 30 and 60 min of incubation respectively, and was delayed at later time points. Plasmalogens and vitamin E (4–25 nmol) mitigated the decreases in 16:0/[3H]20:4-PC (100 nmol) induced by 2 mM AAPH in a similar manner. The initial rate of degradation of intrachain double bonds of 16:0/20:4-PC and 16:0/18:2-PC (320 nmol; 2 mM AAPH) was decreased by 59% and 81% respectively in the presence of 80 nmol of brain lyso-P-PE. In conclusion, plasmalogens markedly delay the oxidative degradation of intrachain double bonds under in vitro conditions. Interactions of enol ether double bonds with initiating peroxyl radicals as well as with products generated by prior oxidation of polyunsaturated fatty acids are proposed to be responsible for this capacity of plasmalogens. Furthermore, the products of enol ether oxidation apparently do not propagate the oxidation of polyunsaturated fatty acids.

Folding of copper proteins: role of the metal?

2018 ◽  
Vol 51 ◽  
Author(s):  
Candan Ariöz ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Metal Ion ◽  
Copper Ions ◽  
Structural Parameters ◽  
Copper Transport ◽  
Transport Systems ◽  
Copper Binding ◽  
Copper Proteins ◽  
Exchange Reactions

AbstractCopper is a redox–active transition metal ion required for the function of many essential human proteins. For biosynthesis of proteins coordinating copper, the metal may bind before, during or after folding of the polypeptide. If the metal binds to unfolded or partially folded structures of the protein, such coordination may modulate the folding reaction. The molecular understanding of how copper is incorporated into proteins requires descriptions of chemical, thermodynamic, kinetic and structural parameters involved in the formation of protein–metal complexes. Because free copper ions are toxic, living systems have elaborate copper-transport systems that include particular proteins that facilitate efficient and specific delivery of copper ions to target proteins. Therefore, these pathways become an integral part of copper protein folding in vivo. This review summarizes biophysical-molecular in vitro work assessing the role of copper in folding and stability of copper-binding proteins as well as protein–protein copper exchange reactions between human copper transport proteins. We also describe some recent findings about the participation of copper ions and copper proteins in protein misfolding and aggregation reactions in vitro.

scholarly journals Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

2021 ◽  
Vol 22 (18) ◽  
pp. 10062
Author(s):  
Madamanchi Geethangili ◽  
Chiao-Wei Lin ◽  
Harry J. Mersmann ◽  
Shih-Torng Ding
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Liver ◽  
Lipid Oxidation ◽  
Signaling Pathway ◽  
Fatty Acid Synthase ◽  
Coenzyme A ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.

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