scholarly journals Vipera berus berus Venom from Russia: Venomics, Bioactivities and Preclinical Assessment of Microgen Antivenom

Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 90 ◽  
Author(s):  
Ruslan I. Al-Shekhadat ◽  
Ksenia S. Lopushanskaya ◽  
Álvaro Segura ◽  
José María Gutiérrez ◽  
Juan J. Calvete ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Secretory Protein ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Vipera Berus ◽  
Phospholipases A2 ◽  
Toxin Binding ◽  
Main Effects

The common European adder, Vipera berus berus, is a medically relevant species, which is widely distributed in Russia and thus, is responsible for most snakebite accidents in Russia. We have investigated the toxic and enzymatic activities and have determined the proteomic composition of its venom. Phospholipases A2 (PLA2, 25.3% of the venom proteome), serine proteinases (SVSP, 16.2%), metalloproteinases (SVMP, 17.2%), vasoactive peptides (bradykinin-potentiating peptides (BPPs), 9.5% and C-type natriuretic peptides (C-NAP, 7.8%), cysteine-rich secretory protein (CRISP, 8%) and L-amino acid oxidase (LAO, 7.3%) represent the major toxin classes found in V. b. berus (Russia) venom. This study was also designed to assess the in vivo and in vitro preclinical efficacy of the Russian Microgen antivenom in neutralizing the main effects of V. b. berus venom. The results show that this antivenom is capable of neutralizing the lethal, hemorrhagic and PLA2 activities. Third-generation antivenomics was applied to quantify the toxin-recognition landscape and the maximal binding capacity of the antivenom for each component of the venom. The antivenomics analysis revealed that 6.24% of the anti-V. b. berus F(ab’)2 molecules fraction are toxin-binding antibodies, 60% of which represent clinically relevant antivenom molecules.

scholarly journals Snake venomics of Bothrops punctatus, a semi-arboreal pitviper species from Antioquia, Colombia

2013 ◽  
Author(s):  
Maritza Fernández Culma ◽  
Jaime A Pereañez ◽  
Vitelbina Núñez Rangel ◽  
Bruno Lomonte
Keyword(s):  
Amino Acid ◽  
Protein Composition ◽  
Secretory Proteins ◽  
Acid Oxidase ◽  
Crude Venom ◽  
Amino Acid Oxidase ◽  
Analytical Strategy ◽  
Phospholipases A2 ◽  
Snake Venomics

Bothrops punctatus is an endangered, semi-arboreal pitviper species distributed in Panamá, Colombia, and Ecuador, whose venom is poorly characterized. In the present work, the protein composition of this venom was profiled using the 'snake venomics' analytical strategy. Decomplexation of the crude venom by RP-HPLC and SDS-PAGE, followed by tandem mass spectrometry of tryptic digests, showed that it consists of proteins assigned to at least nine snake toxin families. Metalloproteinases are predominant in this secretion (41.5% of the total proteins), followed by C-type lectin/lectin-like proteins (16.7%), bradykinin-potentiating peptides (10.7%), phospholipases A2 (9.3%), serine proteinases (5.4%), disintegrins (3.8%), L-amino acid oxidases (3.1%), vascular endothelial growth factors (1.7%), and cysteine-rich secretory proteins (1.2%). Altogether, 6.6% of the proteins were not identified. In vitro, the venom exhibited proteolytic, phospholipase A2, and L-amino acid oxidase activities, as well as angiotensin-converting enzyme (ACE)-inhibitory activity, in agreement with the obtained proteomic profile. Cytotoxic activity on murine C2C12 myoblasts was negative, suggesting that the majority of venom phospholipases A2 likely belong to the acidic type, which often lack major toxic effects. The protein composition of B. punctatus venom shows a good correlation with toxic activities here and previously reported, and adds further data in support of the wide diversity of strategies that have evolved in snake venoms to subdue prey, as increasingly being revealed by proteomic analyses.

scholarly journals Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Benjamin Steinhorn ◽  
Andrea Sorrentino ◽  
Sachin Badole ◽  
Yulia Bogdanova ◽  
Vsevolod Belousov ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hydrogen Peroxide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Systolic Dysfunction ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Organ Systems

AbstractOxidative stress plays an important role in the pathogenesis of many disease states. In the heart, reactive oxygen species are linked with cardiac ischemia/reperfusion injury, hypertrophy, and heart failure. While this correlation between ROS and cardiac pathology has been observed in multiple models of heart failure, the independent role of hydrogen peroxide (H2O2) in vitro and in vivo is unclear, owing to a lack of tools for precise manipulation of intracellular redox state. Here we apply a chemogenetic system based on a yeast D-amino acid oxidase to show that chronic generation of H2O2 in the heart induces a dilated cardiomyopathy with significant systolic dysfunction. We anticipate that chemogenetic approaches will enable future studies of in vivo H2O2 signaling not only in the heart, but also in the many other organ systems where the relationship between redox events and physiology remains unclear.

scholarly journals Protective Role of d-Amino Acid Oxidase against Staphylococcus aureus Infection

2012 ◽  
Vol 80 (4) ◽  
pp. 1546-1553 ◽  
Author(s):  
Hideaki Nakamura ◽  
Jun Fang ◽  
Hiroshi Maeda
Keyword(s):  
Hydrogen Peroxide ◽  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Bactericidal Activity ◽  
Hypochlorous Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Content Type

ABSTRACTd-Amino acid oxidase (DAO) is a hydrogen peroxide-generating enzyme that uses ad-amino acid as a substrate. We hypothesized that DAO may protect against bacterial infection, because hydrogen peroxide is one of the most important molecules in the antibacterial defense systems in mammals. We show here that DAO suppressed the growth ofStaphylococcus aureusin a manner that depended on the concentration of DAO andd-amino acidin vitro. Addition of catalase abolished the bacteriostatic activity of DAO. Although DAO plusd-Ala showed less bactericidal activity, addition of myeloperoxidase (MPO) greatly enhanced the bactericidal activity of DAO. Furthermore, DAO was able to utilize bacterial lysate, which containsd-Ala derived from peptidoglycan; this could produce hydrogen peroxide with, in the presence of myeloperoxidase, formation of hypochlorous acid. This concerted reaction of DAO and MPO led to the bactericidal action.In vivoexperiments showed that DAO−/−(mutant) mice were more susceptible toS. aureusinfection than were DAO+/+(wild-type) mice. These results suggest that DAO, together with myeloperoxidase, may play an important role in antibacterial systems in mammals.

scholarly journals Snake venomics of Bothrops punctatus, a semi-arboreal pitviper species from Antioquia, Colombia

2013 ◽  
Author(s):  
Maritza Fernández Culma ◽  
Jaime A Pereañez ◽  
Vitelbina Núñez Rangel ◽  
Bruno Lomonte
Keyword(s):  
Amino Acid ◽  
Protein Composition ◽  
Secretory Proteins ◽  
Acid Oxidase ◽  
Crude Venom ◽  
Amino Acid Oxidase ◽  
Analytical Strategy ◽  
Phospholipases A2 ◽  
Snake Venomics

Bothrops punctatus is an endangered, semi-arboreal pitviper species distributed in Panamá, Colombia, and Ecuador, whose venom is poorly characterized. In the present work, the protein composition of this venom was profiled using the 'snake venomics' analytical strategy. Decomplexation of the crude venom by RP-HPLC and SDS-PAGE, followed by tandem mass spectrometry of tryptic digests, showed that it consists of proteins assigned to at least nine snake toxin families. Metalloproteinases are predominant in this secretion (41.5% of the total proteins), followed by C-type lectin/lectin-like proteins (16.7%), bradykinin-potentiating peptides (10.7%), phospholipases A2 (9.3%), serine proteinases (5.4%), disintegrins (3.8%), L-amino acid oxidases (3.1%), vascular endothelial growth factors (1.7%), and cysteine-rich secretory proteins (1.2%). Altogether, 6.6% of the proteins were not identified. In vitro, the venom exhibited proteolytic, phospholipase A2, and L-amino acid oxidase activities, as well as angiotensin-converting enzyme (ACE)-inhibitory activity, in agreement with the obtained proteomic profile. Cytotoxic activity on murine C2C12 myoblasts was negative, suggesting that the majority of venom phospholipases A2 likely belong to the acidic type, which often lack major toxic effects. The protein composition of B. punctatus venom shows a good correlation with toxic activities here and previously reported, and adds further data in support of the wide diversity of strategies that have evolved in snake venoms to subdue prey, as increasingly being revealed by proteomic analyses.

In vivo and in vitro expression of porcine D-amino acid oxidase: in vitro system for the synthesis of a functional enzyme

Biochemistry ◽  
1988 ◽  
Vol 27 (18) ◽  
pp. 6693-6697 ◽  
Author(s):  
Kiyoshi Fukui ◽  
Kyoko Momoi ◽  
Fusao Watanabe ◽  
Yoshihiro Miyake
Keyword(s):  
Amino Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
In Vitro System ◽  
In Vitro Expression

scholarly journals From birth to adulthood: An analysis of the Brazilian lancehead (Bothrops moojeni) venom at different life stages

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253050
Author(s):  
Daniela Miki Hatakeyama ◽  
Lídia Jorge Tasima ◽  
Nathália da Costa Galizio ◽  
Caroline Serino-Silva ◽  
Caroline Fabri Bittencourt Rodrigues ◽  
...  
Keyword(s):  
Health Hazard ◽  
Lethal Dose ◽  
Acid Oxidase ◽  
Life Stages ◽  
Ontogenetic Changes ◽  
Amino Acid Oxidase ◽  
Age Related ◽  
Bothrops Moojeni

The Brazilian lancehead (Bothrops moojeni) has a wide distribution in Brazil and represents a serious public health hazard. Previous works reported that the symptoms of snakebites caused by B. moojeni juveniles’ bites were mainly related to coagulation, while those caused by adults’ bites had a more prominent local damage. In this work, we analyzed the venoms of B. moojeni at different life stages to better understand the ontogeny shift in this species. Snakes were grouped by age and sex, and venom pools were formed accordingly. Compositional analyses by one-dimensional electrophoresis (1-DE), chromatography, and mass spectrometry revealed that ontogenetic changes might be mostly related to phospholipase A2 (PLA2) and metalloproteases. Regarding the venoms functional aspect, proteolytic, L-amino acid oxidase, PLA2, and coagulant in vitro activities were assayed, but only the first and the last ones showed age-related changes, with the venom of snakes up to 1 year-old displaying lower proteolytic and higher coagulant activities, while those from 2 years-old onward presented the opposite relation. The venoms of 3 years-old snakes were exceptions to the compositional and functional pattern of adults as both venoms presented profiles similar to neonates. Sex-related differences were observed in specific groups and were not age-related. In vivo experiments (median lethal dose and hemorrhagic activity) were statistically similar between neonates and adults, however we verified that the adult venom killed mice faster comparing to the neonates. All venoms were mostly recognized by the antibothropic serum and displayed similar profiles to 1-DE in western blotting. In conclusion, the Brazilian lancehead venom showed ontogenetic shift in its composition and activities. Furthermore, this change occurred in snakes from 1 to 2 years-old, and interestingly the venom pools from 3 years-old snakes had particular characteristics, which highlights the importance of comprehensive studies to better understand venom variability.

In vitro and in vivo pharmacological profile of AS057278, a selective d-amino acid oxidase inhibitor with potential anti-psychotic properties

2008 ◽  
Vol 18 (3) ◽  
pp. 200-214 ◽  
Author(s):  
Tiziana Adage ◽  
Anne-Cécile Trillat ◽  
Anna Quattropani ◽  
Dominique Perrin ◽  
Laurent Cavarec ◽  
...  
Keyword(s):  
Amino Acid ◽  
Oxidase Inhibitor ◽  
Acid Oxidase ◽  
Anti Psychotic ◽  
Pharmacological Profile ◽  
Amino Acid Oxidase

In Vitro and in Vivo Comparison of Binding of 99m-Tc-Iabeled Anti-CEA MAb F33-104 with 99m-Tc-labeled Anti-CEA MAb BW431/26

1999 ◽  
Vol 38 (04) ◽  
pp. 115-119
Author(s):  
N. Oriuchi ◽  
S. Sugiyama ◽  
M. Kuroki ◽  
Y. Matsuoka ◽  
S. Tanada ◽  
...  
Keyword(s):  
Nude Mice ◽  
Binding Capacity ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Cell Binding ◽  
Vitro Binding ◽  
Labeling Method ◽  
Human Colon Adenocarcinoma

Summary Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tclabeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 107 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tcactivity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

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