Dual Function of a Bee Venom Serine Protease: Prophenoloxidase-Activating Factor in Arthropods and Fibrin(ogen)olytic Enzyme in Mammals

Choo, Young Moo; Lee, Kwang-Sik; Yoon, Hyung Joo; Kim, Bo Yeon; Sohn, Mi Ri; Roh, Jong Yul; Je, Yeon Ho; Kim, Nam Jung; Kim, Iksoo; Woo, Soo Dong; Sohn, Hung Dae; Jin, Byung Rae

doi:10.1371/journal.pone.0010393

Cited by 90 publications

(71 citation statements)

References 54 publications

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“…The findings that Bi-VSP activates prothrombin and that Bi-VSP also acts as a fibrin(ogen)olytic protease [13] suggest that Bi-VSP is used to facilitate the spread of bee venom throughout the bloodstream, as has been demonstrated for snake venom fibrin(ogen)olytic enzymes, which remove fibrinogen effectively and, thereby, reduce blood viscosity [23], [24]. Given the similarity in plasmin targeting with textilinin-1, an anti-bleeding agent [7]–[9], Bi-KTI is likely to be an antifibrinolytic agent that reduces bleeding at the sting site of victims.…”

Section: Resultsmentioning

confidence: 96%

Antifibrinolytic Role of a Bee Venom Serine Protease Inhibitor That Acts as a Plasmin Inhibitor

et al. 2012

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Bee venom is a rich source of pharmacologically active substances. In this study, we identified a bumblebee (Bombus ignitus) venom Kunitz-type serine protease inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an antifibrinolytic agent; however, this inhibitory ability was two-fold weaker than that of aprotinin. The fibrin(ogen)olytic activities of B. ignitus venom serine protease (Bi-VSP) and plasmin in the presence of Bi-KTI indicate that Bi-KTI targets plasmin more specifically than Bi-VSP. These findings demonstrate a novel mechanism by which bumblebee venom affects the hemostatic system through the antifibrinolytic activity of Bi-KTI and through Bi-VSP-mediated fibrin(ogen)olytic activities, raising interest in Bi-KTI and Bi-VSP as potential clinical agents.

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Section: Resultsmentioning

confidence: 96%

Antifibrinolytic Role of a Bee Venom Serine Protease Inhibitor That Acts as a Plasmin Inhibitor

et al. 2012

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“…Another serine protease of this family, named Bi-VSP, has a dual behavior, since in arthropods it triggers the phenoloxidase cascade inducing a lethal immune response, while in mammals it acts as a toxic thrombin-like and plasmin-like fibrinolytic protease (Choo et al, 2010). …”

Section: Bee Venommentioning

confidence: 99%

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products

et al. 2017

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Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.

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“…Bumblebee venom contains several toxic proteins and peptides, including bombolitin, phospholipase A 2 , serine proteases, and serine protease inhibitors (Xin et al, 2009;Choo et al, 2010aChoo et al, , b, 2012Qiu et al, 2011). Recent studies have been demonstrated that bumblebee venom serine proteases and serine protease inhibitors act as fibrin(ogen)olytic agents (Choo et al, 2010b;Qiu et al, 2011) and antifibrinolytic agents (Choo et al, 2012), respectively. Serine protease inhibitors are ubiquitous in numerous tissues and organisms, including animals, plants, and microbes.…”

Section: Introductionmentioning

confidence: 99%

Molecular Cloning and Characterization of Chymotrypsin Inhibitor and Chitin-Binding Protein Homologs from the Bumblebee Bombus terrestris

Qiu¹,

Yoon²,

Jin³

2012

International Journal of Industrial Entomology

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The bumblebee Bombus terrestris is widely used in greenhouses to pollinate crops. Here, we report the molecular cloning and characterization of chymotrypsin inhibitor and chitin-binding protein homologs from B. terrestris. Two cDNAs encoding chymotrypsin inhibitor (Bt-CI) and chitin-binding protein (Bt-CBP) homologs were cloned from B. terrestris. Gene sequence analysis showed that Bt-CI gene consists of three exons encoding 75 amino acids, including a predicted 20-amino acid signal peptide, while Bt-CBP consists of two exons encoding 78 amino acids, including a predicted 26-amino acid signal peptide. The mature Bt-CI and Bt-CBP peptides contain ten and six conserved cysteine residues, respectively. Database searches using the deduced sequences of Bt-CI and Bt-CBP showed similarity to those from B. impatiens (96% peptide sequence identities). Bt-CI and Bt-CBP were expressed in both the venom gland and fat body of B. terrestris worker bees. The recombinant Bt-CI and Bt-CBP peptides were expressed in baculovirusinfected insect cells. Taken together, our findings describe the molecular characterization of Bt-CI and Bt-CBP from B. terrestris.

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Dual Function of a Bee Venom Serine Protease: Prophenoloxidase-Activating Factor in Arthropods and Fibrin(ogen)olytic Enzyme in Mammals

Cited by 90 publications

References 54 publications

Antifibrinolytic Role of a Bee Venom Serine Protease Inhibitor That Acts as a Plasmin Inhibitor

Antifibrinolytic Role of a Bee Venom Serine Protease Inhibitor That Acts as a Plasmin Inhibitor

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products

Molecular Cloning and Characterization of Chymotrypsin Inhibitor and Chitin-Binding Protein Homologs from the Bumblebee Bombus terrestris

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