Abstract
Bee venom contains a variety of peptides and enzymes, including serine proteases. While the presence of serine proteases in bee venom has been demonstrated, the role of these proteins in bee venom has not been elucidated. Furthermore, there is currently no information available regarding the melanization response or the fibrin(ogen)olytic activity of bee venom serine protease, and the molecular mechanism of its action remains unknown. Here we show that bee venom serine protease (Bi-VSP) is a multifunctional enzyme. In insects, Bi-VSP acts as an arthropod prophenoloxidase (proPO)-activating factor (PPAF), thereby triggering the phenoloxidase (PO) cascade. Bi-VSP injected through the stinger induces a lethal melanization response in target insects by modulating the innate immune response. In mammals, Bi-VSP acts similarly to snake venom serine protease, which exhibits fibrin(ogen)olytic activity. Bi-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products, defining roles for Bi-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings provide a novel view of the mechanism of bee venom in which the bee venom serine protease kills target insects via a melanization strategy and exhibits fibrin(ogen)olytic activity.
Highlights
Bee venom serves as a defensive weapon against intruders, and it contains a variety of enzymes, peptides, and biogenic amines [1,2,3,4]
To explore the role of serine proteases in bee venom, we identified an expressed sequence tag (EST) for a gene encoding a venom serine protease (Bi-VSP) in the bumblebee Bombus ignitus
We examined the pattern of Bi-VSP expression to confirm that it is a component of bee venom
Summary
Bee venom serves as a defensive weapon against intruders (such as animals), and it contains a variety of enzymes, peptides, and biogenic amines [1,2,3,4]. Bee stings can cause life-threatening allergic reactions due to an immediate hypersensitivity-induced reaction that leads to anaphylaxis [5,6]. The amount of venom released by a honeybee sting is approximately 5-times greater than that released by a bumblebee sting [8]. Bee venom has been used as a traditional medicine to treat a variety of diseases, including arthritis, rheumatism, pain, cancerous tumors, and skin diseases [4,9]. Better knowledge of the components of bee venom would be useful for improving therapeutic treatments for allergic reactions to bee stings [1], developing an immunotherapy for bee venom hypersensitivity [6,10], and investigating the mechanism underlying venom therapy in alternative medicine [4,11]
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