Proteomic and toxinological characterization of the venom of the South African Ringhals cobra Hemachatus haemachatus
Fecha
2018-06
Tipo
artículo original
Autores
Sánchez Brenes, Andrés
Herrera Vega, María
Villalta Arrieta, Mauren
Solano Centeno, Daniela
Segura Ruiz, Álvaro
Lomonte, Bruno
Gutiérrez, José María
León Montero, Guillermo
Vargas Arroyo, Mariángela
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Resumen
The protein composition and toxinological profile of the venom of the African spitting elapid Hemachatus haemachatus
(Ringhals) were characterized by bottom-up proteomics and functional in vitro and in vivo assays.
Venom is composed of abundant three-finger toxins (3FTxs; 63.3%), followed by phospholipases A2 (PLA2s;
22.8%), snake venom metalloproteinases (SVMPs; 7.1%), cysteine-rich secretory proteins (CRISPs; 4.1%) and
Kunitz type protease inhibitors (KTPIs; 1.5%). 3FTxs are the main responsible for lethality and myotoxicity in
mice and in vitro anticoagulant activity. In contrast to closely related spitting species, whose venom 3FTxs
induces dermonecrosis, the 3FTxs of H. haemachatus did not induce dermonecrotic activity. The venom showed
in vitro PLA2 activity, and most likely PLA2s contribute to some extent in venom lethality, as judged by partial
reduction in toxicity after inhibition of their catalytic activity. Despite its relatively high content of SVMPs,
compared to most elapids, the venom of H. haemachatus did not exert hemorrhagic effect, proteolytic activity on
azocasein or defibrinogenating activity. Toxicovenomic characterization of H. haemachatus venom revealed that
RP-HPLC fractions with higher abundance of 3FTxs presented lethal activity, while fractions with high content of
PLA2s did not, underscoring the role of 3FTxs in the pathophysiology caused by this venom.
Biological significance: The proteomic composition and toxinological profile of the venom of Ringhals snake,
Hemachatus haemachatus, a cobra-like spitting snake endemic to southern Africa, were investigated. In vitro,
Ringhals venom showed anticoagulant and phospholipase A2 activities, but was devoid of proteolytic activity on
azocasein. In mice, venom induced lethality and myotoxicity, but no local hemorrhage or dermonecrosis. The
lack of dermonecrotic activity is in sharp contrast to venoms of closely related spitting cobras which present a
similar relative abundance of 3FTxs but are potently dermonecrotic. 3FTxs, the most abundant protein family in
the venom, are predominantly responsible for toxic effects. PLA2 enzyme inactivation experiments suggest that
H. haemachatus venom lethality is not dependent on PLA2s, but instead is more related to neurotoxic or cardiotoxic
3FTxs. The characterization of this venom, based on proteomic and toxicovenomic approaches, is useful
for more in depth studies associated with biogeography, phylogeny, toxinology and antivenom efficacy towards
the venom of this species, and its association with related elapids
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Palabras clave
Hemachatus haemachatus, Venomics, Ringhals, Three-finger toxins, Phospholipase A2, Snake venom, 615.946 Venenos animales