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Effects of the Heterodimeric Neurotoxic Phospholipase A₂ from the Venom of Vipera nikolskii on the Contractility of Rat Papillary Muscles and Thoracic Aortas.

ABSTRACT: Phospholipases A₂ (PLA₂s) are a large family of snake toxins manifesting diverse biological effects, which are not always related to phospholipolytic activity. Snake venom PLA₂s (svPLA₂s) are extracellular proteins with a molecular mass of 13-14 kDa. They are present in venoms in the form of monomers, dimers, and larger oligomers. The cardiovascular system is one of the multiple svPLA₂ targets in prey organisms. The results obtained previously on the cardiovascular effects of monomeric svPLA₂s were inconsistent, while the data on the dimeric svPLA₂ crotoxin from the rattlesnake Crotalus durissus terrificus showed that it significantly reduced the contractile force of guinea pig hearts. Here, we studied the effects of the heterodimeric svPLA₂ HDP-1 from the viper Vipera nikolskii on papillary muscle (PM) contractility and the tension of the aortic rings (ARs). HDP-1 is structurally different from crotoxin, and over a wide range of concentrations, it produced a long-term, stable, positive inotropic effect in PMs, which did not turn into contractures at the concentrations studied. This also distinguishes HDP-1 from the monomeric svPLA₂s, which at high concentrations inhibited cardiac function. HDP-1, when acting on ARs preconstricted with 10 μM phenylephrine, induced a vasorelaxant effect, similar to some other svPLA₂s. These are the first indications of the cardiac and vascular effects of true vipers' heterodimeric svPLA₂s.

SUBMITTER: Averin A

PROVIDER: S-EPMC10891809 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Effects of the Heterodimeric Neurotoxic Phospholipase A2 from the Venom of Vipera nikolskii on the Contractility of Rat Papillary Muscles and Thoracic Aortas.

Averin Alexey A Starkov Vladislav V Tsetlin Victor V Utkin Yuri Y

Toxins 20240210 2

Phospholipases A2 (PLA2s) are a large family of snake toxins manifesting diverse biological effects, which are not always related to phospholipolytic activity. Snake venom PLA2s (svPLA2s) are extracellular proteins with a molecular mass of 13-14 kDa. They are present in venoms in the form of monomers, dimers, and larger oligomers. The cardiovascular system is one of the multiple svPLA2 targets in prey organisms. The results obtained previous ...[more]

PMID: 38393179

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Project description:BackgroundThe variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA(2) neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA(2) composition of the snakes captured in the same areas.Methodology/principal findingsWe conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA(2)s. We used SELDI technology to study the diversity of PLA(2) in various venom samples. Neurological signs (mainly cranial nerve disturbances) were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA(2)s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA(2) venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains.Conclusions/significanceThe association of epidemiological studies to genetic, biochemical and immunochemical analyses of snake venoms allowed a good evaluation of the potential neurotoxicity of snake bites. A correlation was found between the expression of neurological symptoms in humans and the intensity of the cross-reaction of venoms with anti-ammodytoxin antibodies, which is correlated with the level of neurotoxin (vaspin and/or ammodytoxin) expression in the venom. The origin of the two recently identified neurotoxic snake populations is discussed according to venom PLA(2) genome and transcriptome data.

Dataset Information

Effects of the Heterodimeric Neurotoxic Phospholipase A₂ from the Venom of Vipera nikolskii on the Contractility of Rat Papillary Muscles and Thoracic Aortas.

Publications

Effects of the Heterodimeric Neurotoxic Phospholipase A<sub>2</sub> from the Venom of <i>Vipera nikolskii</i> on the Contractility of Rat Papillary Muscles and Thoracic Aortas.

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