scholarly journals Peptide Inhibitor of Complement C1 Inhibits the Peroxidase Activity of Hemoglobin and Myoglobin

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Pamela S. Hair ◽  
Kenji M. Cunnion ◽  
Neel K. Krishna
Keyword(s):  
Peroxidase Activity ◽  
Degradation Products ◽  
Acid Hydrazide ◽  
Peptide Inhibitor ◽  
Iron Release ◽  
Antioxidant Mechanism ◽  
Hemoglobin Molecule ◽  
Comparable Activity ◽  
Absorbance Peak ◽  
Stress Damage

Hemoglobin is the natural carrier of oxygen in red blood cells (RBCs). While intracellular hemoglobin provides life-sustaining oxygen transport, extracellular free hemoglobin displays toxicity due to inherent peroxidase activity generating reactive oxygen species that subsequently react with the hemoglobin molecule to produce toxic heme degradation products resulting in free radicals, oxidative stress damage, and lipid peroxidation. We have recently demonstrated that Peptide Inhibitor of Complement C1 (PIC1) inhibits peroxidase activity of the heme-based enzyme myeloperoxidase. To elucidate whether PIC1 could inhibit peroxidase activity of hemoglobin, we evaluated the consequence of PIC1 on RBC lysates, methemoglobin, and myoglobin using tetramethylbenzidine (TMB) as an oxidation target. PIC1 reversibly and dose-dependently prevented TMB oxidation to tetramethylbenzidine diimine by RBC lysates, methemoglobin, and myoglobin, having comparable activity to the inhibitor 4-aminobenzoic acid hydrazide. PIC1 inhibited TMB oxidation of RBC lysates similar to L-cysteine suggesting that the two cysteine residues contained in PIC1 may mediate peroxidase activity. PIC1 also inhibited heme destruction by NaOCl for RBC lysates, hemoglobin, and myoglobin as assayed by preservation of the Soret absorbance peak in the presence of NaOCl and reduction in free iron release. In conclusion, PIC1 inhibits peroxidase activity of hemoglobin and myoglobin likely via an antioxidant mechanism.

scholarly journals The Protective Effects of Carrageenan Oligosaccharides on Intestinal Oxidative Stress Damage of Female Drosophila melanogaster

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1996
Author(s):  
Kun Yang ◽  
Qiaowei Li ◽  
Guocai Zhang ◽  
Chao Ma ◽  
Xianjun Dai
Keyword(s):  
Oxidative Stress ◽  
High Throughput Sequencing ◽  
Antioxidant Activities ◽  
Intestinal Flora ◽  
Antioxidant Defense System ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
H2o2 Treatment ◽  
Antioxidant Mechanism ◽  
Stress Damage

Carrageenan oligosaccharides (COS) have been reported to possess excellent antioxidant activities, but the underlying mechanism remains poorly understood. In this study, H2O2 was applied to trigger oxidative stress. The results showed that the addition of COS could effectively extend the lifespan of female Drosophila, which was associated with improvements by COS on the antioxidant defense system, including a decrease in MDA, the enhanced activities of SOD and CAT, the reduction of ROS in intestinal epithelial cells, and the up-regulation of antioxidant-relevant genes (GCL, GSTs, Nrf2, SOD). Meanwhile, the axenic female Drosophila fed with COS showed almost no improvement in the above measurements after H2O2 treatment, which highlighted the antioxidant mechanism of COS was closely related to intestinal microorganisms. Then, 16S rDNA high-throughput sequencing was applied and the result showed that the addition of COS in diets contributed to the diversity and abundance of intestinal flora in H2O2 induced female Drosophila. Moreover, COS significantly inhibited the expression of gene mTOR, elevated its downstream gene 4E-BP, and further inhibited autophagy-relevant genes (AMPKα, Atg1, Atg5, Atg8a) in H2O2 induced female Drosophila. The inhibition of the mTOR pathway and the activation of autophagy was probably mediated by the antioxidant effects of COS. These results provide potential evidence for further understanding of COS as an intestinal antioxidant.

scholarly journals Rational design of a potent macrocyclic peptide inhibitor targeting the PD-1/PD-L1 protein–protein interaction

RSC Advances ◽  
2021 ◽  
Vol 11 (38) ◽  
pp. 23270-23279
Author(s):  
Qi Miao ◽  
Wanheng Zhang ◽  
Kuojun Zhang ◽  
He Li ◽  
Jidong Zhu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Protein Interaction ◽  
Rational Design ◽  
Peptide Inhibitor ◽  
Protein Protein Interaction ◽  
Comparable Activity ◽  
L1 Protein ◽  
Macrocyclic Peptide

The co-crystal structure and CADD-guided rational design of JMPDP-027 which has comparable activity to mAb in both in vitro and in vivo tests.

scholarly journals Peroxidase activity of erythrocytes hemoglobin under action of low-frequency vibration

2021 ◽  
Vol 15 (4) ◽  
pp. 3-16
Author(s):  
O. I. Dotsenko ◽  
◽  
G. V. Taradina ◽  
А. М. Mischenko ◽  
◽  
...  
Keyword(s):  
Kinetic Parameters ◽  
Peroxidase Activity ◽  
Structural Changes ◽  
Low Frequency ◽  
Oxidation Reactions ◽  
Frequency Range ◽  
Oxidative Potential ◽  
Peroxidase Reaction ◽  
Low Frequency Vibration ◽  
Hemoglobin Molecule

Background. Hemoglobin is a hemoprotein which in the presence of oxidative equivalents, such as H2O2, can act as peroxidase with a very high oxidative potential. Hemoglobin oxidation is accompanied by generation of highly oxidized forms of iron and globin radicals that have high oxidative activity and are toxic to cells. In addition, peroxidase activity may indicate structural changes that occur in the hemoglobin molecule as a result of chemical modification. Materials and Methods. Erythrocyte suspension was subjected to vibration for 3 h within the frequency range from 8 to 32 Hz with amplitudes of 0.5 ± 0.04 and 0.9 ± 0.08 mm. At certain intervals, hemoglobin peroxidase activity was determined together with the content of its ligand forms in the hemolysates of cells. Additionally, experiments were performed to investigate the mechanism and calculate the kinetic parameters of peroxidase reaction. Results and Discussion. Experimental data on low-frequency vibrations effect on erythrocyte hemoglobin peroxidase activity were analyzed. The kinetics of the oxidation reaction of p-phenylenediamine by hemoglobin in erythrocytes was studied. It was found that peroxidase oxidation has a ping-pong mechanism. The kinetic parameters of the peroxidase reaction involving hemoglobin were determined. The change of kinetic parameters after two-hour exposure to the incubation medium and low-frequency vibration was studied. A possible mechanism of action of hemoglobin in oxidation reactions involving H2O2 was proposed. Conclusion. Any effect that initiates the formation of methemoglobin leads to an increase in the peroxidase activity of hemoglobin due to the involvement of the latter in the pseudoperoxidase cycle and the formation of toxic reactive globin radicals. The high content of oxyhemoglobin in the cell, observed under vibrations within the frequency range of 16–32 Hz with an amplitude of 0.9 ± 0.08 mm, can prevent its oxidation and involvement in the pseudoperoxidase cycle.

scholarly journals Efficient antioxidant defence systems of spring barley in response to stress induced jointly by the cyst nematode parasitism and cadmium exposure

2020 ◽  
Vol 456 (1-2) ◽  
pp. 189-206
Author(s):  
Mateusz Labudda ◽  
Ewa Muszyńska ◽  
Marta Gietler ◽  
Elżbieta Różańska ◽  
Anna Rybarczyk-Płońska ◽  
...  
Keyword(s):  
Reductase Activity ◽  
Spring Barley ◽  
Superoxide Anions ◽  
Antioxidant Mechanism ◽  
Cadmium Treatment ◽  
Protein Functions ◽  
Barley Leaves ◽  
Response To Stress ◽  
Nematode Parasitism ◽  
Stress Damage

Abstract Aims This research aimed to establish how Hordeum vulgare responds to abiotic and biotic stress affecting in tandem. Methods Plants were inoculated with Heterodera filipjevi and treated with cadmium (Cd) concentration (5 μM) that can occur in the cultivated soil. To verify the hypothesis about participation of increased antioxidative defence in H. vulgare under stress, biochemical and microscopic methods were implemented. Results The amount of superoxide anions and hydrogen peroxide was diminished in plants that were both nematode-inoculated and cadmium-treated. Superoxide anions were rendered harmless by increased activity of superoxide dismutase, and H2O2 was scavenged via Foyer-Halliwell-Asada pathway. The unique enhanced antioxidant capacity of double stressed plants was also linked with the accumulation of S-nitrosoglutathione as nitrosoglutathione reductase activity was inhibited. Furthermore, stimulated activity of arginase in these plants could promote polyamine synthesis and indirectly enhance non-enzymatic antioxidant mechanism. Results indicate that different antioxidants operating together significantly restricted oxidation of lipids and proteins, thus the integrity of cell membranes and protein functions were maintained. Conclusions The ROS deactivation machinery in barley leaves showed an unusual response during stress induced by H. filipjevi infection and cadmium treatment. Plants could induce a multi-component model of stress response, to detoxify Cd ions and efficiently repair stress damage.

Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes

2005 ◽  
Vol 24 (1) ◽  
pp. 63-70 ◽  
Author(s):  
M. Fichter ◽  
U. Körner ◽  
J. Schömburg ◽  
L. Jennings ◽  
A. A. Cole ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Articular Chondrocytes ◽  
Degradation Products ◽  
Collagen Degradation ◽  
Collagen Degradation Products

Structural Studies of Fibrinolysis by Electron and Light Microscopy

1999 ◽  
Vol 82 (08) ◽  
pp. 277-282 ◽  
Author(s):  
Yuri Veklich ◽  
Jean-Philippe Collet ◽  
Charles Francis ◽  
John W. Weisel
Keyword(s):  
Electron Microscopy ◽  
Light Microscopy ◽  
Plasminogen Activator ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Degradation Products ◽  
Molecular Model ◽  
Three Dimensional ◽  
Tissue Type ◽  
Type Plasminogen Activator

IntroductionMuch is known about the fibrinolytic system that converts fibrin-bound plasminogen to the active protease, plasmin, using plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator. Plasmin then cleaves fibrin at specific sites and generates soluble fragments, many of which have been characterized, providing the basis for a molecular model of the polypeptide chain degradation.1-3 Soluble degradation products of fibrin have also been characterized by transmission electron microscopy, yielding a model for their structure.4 Moreover, high resolution, three-dimensional structures of certain fibrinogen fragments has provided a wealth of information that may be useful in understanding how various proteins bind to fibrin and the overall process of fibrinolysis (Doolittle, this volume).5,6 Both the rate of fibrinolysis and the structures of soluble derivatives are determined in part by the fibrin network structure itself. Furthermore, the activation of plasminogen by t-PA is accelerated by the conversion of fibrinogen to fibrin, and this reaction is also affected by the structure of the fibrin. For example, clots made of thin fibers have a decreased rate of conversion of plasminogen to plasmin by t-PA, and they generally are lysed more slowly than clots composed of thick fibers.7-9 Under other conditions, however, clots made of thin fibers may be lysed more rapidly.10 In addition, fibrin clots composed of abnormally thin fibers formed from certain dysfibrinogens display decreased plasminogen binding and a lower rate of fibrinolysis.11-13 Therefore, our increasing knowledge of various dysfibrinogenemias will aid our understanding of mechanisms of fibrinolysis (Matsuda, this volume).14,15 To account for these diverse observations and more fully understand the molecular basis of fibrinolysis, more knowledge of the physical changes in the fibrin matrix that precede solubilization is required. In this report, we summarize recent experiments utilizing transmission and scanning electron microscopy and confocal light microscopy to provide information about the structural changes occurring in polymerized fibrin during fibrinolysis. Many of the results of these experiments were unexpected and suggest some aspects of potential molecular mechanisms of fibrinolysis, which will also be described here.

Fibrinogen Bastia (γ 318 Asp → Tyr) a Novel Abnormal Fibrinogen Characterized by Defective Fibrin Polymerization

1999 ◽  
Vol 82 (12) ◽  
pp. 1639-1643 ◽  
Author(s):  
Karim Chabane Lounes ◽  
Claudine Soria ◽  
Antoine Valognes ◽  
Marie France Turchini ◽  
Jaap Koopman ◽  
...  
Keyword(s):  
Calcium Ions ◽  
Clinical Symptoms ◽  
Degradation Products ◽  
Base Substitution ◽  
Chain Gene ◽  
Fibrinogen Concentration ◽  
Clotting Time ◽  
Terminal Part ◽  
Fibrin Polymerization ◽  
Chain Sequence

SummaryA new congenital dysfibrinogen, Fibrinogen Bastia, was discovered in a 20-year-old woman with no clinical symptoms. The plasma thrombin-clotting time was severely prolonged. The functional plasma fibrinogen concentration was low (0.2 mg/ml), whereas the immunological concentration was normal (2.9 mg/ml). Purified fibrinogen Bastia displayed a markedly prolonged thrombin-clotting time related to a delayed thrombin-induced fibrin polymerization. Both the thrombin-clotting time and the fibrin polymerization were partially corrected by the addition of calcium ions. The anomaly of fibrinogen Bastia was found to be located in the γ-chain since by SDS-PAGE performed according to the method of Laemmli two γ-chains were detected, one normal and one with an apparently lower molecular weight. Furthermore, analysis of plasmin degradation products demonstrated that calcium ions only partially protect fibrinogen Bastia γ-chain against plasmin digestion, suggesting that the anomaly is located in the C-terminal part of the γ-chain. Sequence analysis of PCR-amplified genomic DNA fragments of the propositus demonstrated a single base substitution (G → T) in the exon VIII of the γ chain gene, resulting in the amino acid substitution 318 Asp (GAC) → Tyr (TAC). The PCR clones were recloned and 50% of them contained the mutation, indicating that the patient was heterozygous. These data indicate that residue Asp 318 is important for normal fibrin polymerization and the protective effect of calcium ions against plasmin degradation of the C-terminal part of the γ-chain.

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