The Experts below are selected from a list of 14727 Experts worldwide ranked by ideXlab platform
Byung Rae Jin - One of the best experts on this subject based on the ideXlab platform.
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antimicrobial activity of a honeybee apis cerana venom kazal type Serine Protease Inhibitor
Toxicon, 2013Co-Authors: Bo Yeon Kim, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Fengming Zou, Yongsoo Choi, Hyung Wook Kwon, Byung Rae JinAbstract:Insect-derived Kazal-type Serine Protease Inhibitors exhibit thrombin, elastase, plasmin, proteinase K, or subtilisin A inhibition activity, but so far, no functional roles for bee-derived Kazal-type Serine Protease Inhibitors have been identified. In this study, a bee (Apis cerana) venom Kazal-type Serine Protease Inhibitor (AcKTSPI) that acts as a microbial Serine Protease Inhibitor was identified. AcKTSPI contained a single Kazal domain that displayed six conserved cysteine residues and a P1 threonine residue. AcKTSPI was expressed in the venom gland and was present as a 10-kDa peptide in bee venom. Recombinant AcKTSPI Kazal domain (AcKTSPI-Kd) expressed in baculovirus-infected insect cells demonstrated Inhibitory activity against subtilisin A (Ki 67.03 nM) and proteinase K (Ki 91.53 nM), but not against α-chymotrypsin or trypsin, which implies a role for AcKTSPI as a microbial Serine Protease Inhibitor. However, AcKTSPI-Kd exhibited no detectable Inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or elastase. Additionally, AcKTSPI-Kd bound directly to Bacillus subtilis, Bacillus thuringiensis, Beauveria bassiana, and Fusarium graminearum but not to Escherichia coli. Consistent with these findings, AcKTSPI-Kd showed antibacterial activity against Gram-positive bacteria and antifungal activity against both plant-pathogenic and entomopathogenic fungi. These findings constitute molecular evidence that AcKTSPI acts as an Inhibitor of microbial Serine Proteases. This paper provides a novel view of the antimicrobial functions of a bee venom Kazal-type Serine Protease Inhibitor.
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A spider-derived Kunitz-type Serine Protease Inhibitor that acts as a plasmin Inhibitor and an elastase Inhibitor.
PLOS ONE, 2013Co-Authors: Hu Wan, Hyung Joo Yoon, Kwang Sik Lee, Bo Yeon Kim, Fengming Zou, Byung Rae JinAbstract:Kunitz-type Serine Protease Inhibitors are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis, and inflammation. While spider-derived Kunitz-type proteins show activity in trypsin or chymotrypsin inhibition and K+ channel blocking, no additional role for these proteins has been elucidated. In this study, we identified the first spider (Araneus ventricosus) Kunitz-type Serine Protease Inhibitor (AvKTI) that acts as a plasmin Inhibitor and an elastase Inhibitor. AvKTI possesses a Kunitz domain consisting of a 57-amino-acid mature peptide that displays features consistent with Kunitz-type Inhibitors, including six conserved cysteine residues and a P1 lysine residue. Recombinant AvKTI, expressed in baculovirus-infected insect cells, showed a dual Inhibitory activity against trypsin (Ki 7.34 nM) and chymotrypsin (Ki 37.75 nM), defining a role for AvKTI as a spider-derived Kunitz-type Serine Protease Inhibitor. Additionally, AvKTI showed no detectable Inhibitory effects on factor Xa, thrombin, or tissue plasminogen activator; however, AvKTI inhibited plasmin (Ki 4.89 nM) and neutrophil elastase (Ki 169.07 nM), indicating that it acts as an antifibrinolytic factor and an antielastolytic factor. These findings constitute molecular evidence that AvKTI acts as a plasmin Inhibitor and an elastase Inhibitor and also provide a novel view of the functions of a spider-derived Kunitz-type Serine Protease Inhibitor.
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antifibrinolytic role of a bee venom Serine Protease Inhibitor that acts as a plasmin Inhibitor
PLOS ONE, 2012Co-Authors: Young Moo Choo, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Yuling Qiu, Mi Ri Sohn, Hung Dae Sohn, Byung Rae JinAbstract: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.
Christine Mehner - One of the best experts on this subject based on the ideXlab platform.
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abstract 442 Serine Protease Inhibitor kazal type 1 spink1 drives anoikis resistance in ovarian clear cell carcinoma
Cancer Research, 2018Co-Authors: Christine Mehner, Mathew Coban, Alexandra Hockla, Derek C Radisky, Evette S RadiskyAbstract:Patients diagnosed with ovarian cancer face an average 5 year survival rate of 46%; low survival is driven by early and ongoing intraperitoneal dissemination and metastasis of the tumor. Among the different histotypes of ovarian cancer, ovarian clear cell carcinoma (OCCC) has a particularly poor prognosis when diagnosed in late stage, as these tumors tend to be chemoresistant, leaving no effective therapeutic options. Intraperitoneal metastasis requires cells to become anoikis resistant, where apoptosis normally induced by loss of attachment is suppressed. We seek to better understand the mechanisms involved in anoikis resistance in OCCC, which in the future could lead to new therapeutic strategies for these patients. We have found that Serine Protease Inhibitor Kazal type 1 (SPINK1), an endogenous Inhibitor of trypsin like Serine Proteases, is also an important regulator of anoikis resistance in some ovarian cancers. In this study, we aimed to dissect the role of SPINK1 specifically in OCCC, defining its contribution to anoikis resistance using cultured OCCC cell lines and elucidating its mechanism of action. We compared anoikis resistance of cells with endogenous SPINK1 expression versus cells in which SPINK1 was silenced using lentiviral shRNA constructs, when culturing cells on ultra-low attachment plates to mimic cell detachment from the extracellular matrix. We found that knockdown of SPINK1 reduced survival and stimulated apoptotic pathways in OCCC cells grown under detached conditions, implicating SPINK1 in anoikis resistance of OCCC cells. As a secreted Protease Inhibitor, SPINK1 may be expected to confer anoikis resistance by inhibiting an extracellular Serine Protease involved in triggering anoikis. Because many Proteases represent potential targets of SPINK1, we have designed a strategy using Activity Based Protein Profiling (ABPP) to discover the targets of SPINK1 from among this large pool of candidates. In pilot studies, we have successfully used a novel activity-based probe to covalently label the active sites of Serine Proteases secreted from OCCC cells. In ongoing efforts, we are optimizing methods to identify labeled Proteases with high sensitivity using tandem mass spectrometry. We will then identify those Proteases regulated by SPINK1 through comparison of labeled proteomes from OCCC cells with and without SPINK1 treatment,, and candidate Proteases will be further analyzed for their role in triggering anoikis. The identification of SPINK1 regulated Proteases that are responsible for mediating anoikis in our models will give insight into important mechanisms whereby tumor cells acquire resistance to anoikis in OCCC. In-depth understanding of anoikis resistance, a critical component of ovarian cancer progression and metastasis, may lead to novel biomarkers of disease progression as well as important therapeutic targets. Citation Format: Christine Mehner, Mathew A. Coban, Alexandra Hockla, Derek C. Radisky, Evette S. Radisky. Serine Protease Inhibitor Kazal type 1 (SPINK1) drives anoikis resistance in ovarian clear cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 442.
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Serine Protease Inhibitor kazal type 1 spink1 drives proliferation and anoikis resistance in a subset of ovarian cancers
Oncotarget, 2015Co-Authors: Christine Mehner, Alexandra Hockla, Ann L Oberg, Kimberly R Kalli, Aziza Nassar, Devon F Pendlebury, Magdalena A Cichon, Krista M Goergen, Matthew J Maurer, Ellen L GoodeAbstract:// Christine Mehner 1 , Ann L. Oberg 2 , Kimberly R. Kalli 3 , Aziza Nassar 4 , Alexandra Hockla 1 , Devon Pendlebury 1 , Magdalena A. Cichon 1 , Krista M. Goergen 2 , Matthew J. Maurer 2 , Ellen L. Goode 5 , Gary L. Keeney 6 , Aminah Jatoi 3 , Miklos Sahin-Toth 7 , John A. Copland 1 , Derek C. Radisky 1 and Evette S. Radisky 1 1 Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA 2 Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN , USA 3 Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA 4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA 5 Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA 6 Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA 7 Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, USA Correspondence to: Evette S. Radisky, email: // Keywords : SPINK1, ovarian cancer, Serine Protease Inhibitor, EGFR, anoikis Received : July 07, 2015 Accepted : September 14, 2015 Published : September 30, 2015 Abstract Ovarian cancer represents the most lethal tumor type among malignancies of the female reproductive system. Overall survival rates remain low. In this study, we identify the Serine Protease Inhibitor Kazal type 1 (SPINK1) as a potential therapeutic target for a subset of ovarian cancers. We show that SPINK1 drives ovarian cancer cell proliferation through activation of epidermal growth factor receptor (EGFR) signaling, and that SPINK1 promotes resistance to anoikis through a distinct mechanism involving Protease inhibition. In analyses of ovarian tumor specimens from a Mayo Clinic cohort of 490 patients, we further find that SPINK1 immunostaining represents an independent prognostic factor for poor survival, with the strongest association in patients with nonserous histological tumor subtypes (endometrioid, clear cell, and mucinous). This study provides novel insight into the fundamental processes underlying ovarian cancer progression, and also suggests new avenues for development of molecularly targeted therapies.
Hu Wan - One of the best experts on this subject based on the ideXlab platform.
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antimicrobial activity of a honeybee apis cerana venom kazal type Serine Protease Inhibitor
Toxicon, 2013Co-Authors: Bo Yeon Kim, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Fengming Zou, Yongsoo Choi, Hyung Wook Kwon, Byung Rae JinAbstract:Insect-derived Kazal-type Serine Protease Inhibitors exhibit thrombin, elastase, plasmin, proteinase K, or subtilisin A inhibition activity, but so far, no functional roles for bee-derived Kazal-type Serine Protease Inhibitors have been identified. In this study, a bee (Apis cerana) venom Kazal-type Serine Protease Inhibitor (AcKTSPI) that acts as a microbial Serine Protease Inhibitor was identified. AcKTSPI contained a single Kazal domain that displayed six conserved cysteine residues and a P1 threonine residue. AcKTSPI was expressed in the venom gland and was present as a 10-kDa peptide in bee venom. Recombinant AcKTSPI Kazal domain (AcKTSPI-Kd) expressed in baculovirus-infected insect cells demonstrated Inhibitory activity against subtilisin A (Ki 67.03 nM) and proteinase K (Ki 91.53 nM), but not against α-chymotrypsin or trypsin, which implies a role for AcKTSPI as a microbial Serine Protease Inhibitor. However, AcKTSPI-Kd exhibited no detectable Inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or elastase. Additionally, AcKTSPI-Kd bound directly to Bacillus subtilis, Bacillus thuringiensis, Beauveria bassiana, and Fusarium graminearum but not to Escherichia coli. Consistent with these findings, AcKTSPI-Kd showed antibacterial activity against Gram-positive bacteria and antifungal activity against both plant-pathogenic and entomopathogenic fungi. These findings constitute molecular evidence that AcKTSPI acts as an Inhibitor of microbial Serine Proteases. This paper provides a novel view of the antimicrobial functions of a bee venom Kazal-type Serine Protease Inhibitor.
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A spider-derived Kunitz-type Serine Protease Inhibitor that acts as a plasmin Inhibitor and an elastase Inhibitor.
PLOS ONE, 2013Co-Authors: Hu Wan, Hyung Joo Yoon, Kwang Sik Lee, Bo Yeon Kim, Fengming Zou, Byung Rae JinAbstract:Kunitz-type Serine Protease Inhibitors are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis, and inflammation. While spider-derived Kunitz-type proteins show activity in trypsin or chymotrypsin inhibition and K+ channel blocking, no additional role for these proteins has been elucidated. In this study, we identified the first spider (Araneus ventricosus) Kunitz-type Serine Protease Inhibitor (AvKTI) that acts as a plasmin Inhibitor and an elastase Inhibitor. AvKTI possesses a Kunitz domain consisting of a 57-amino-acid mature peptide that displays features consistent with Kunitz-type Inhibitors, including six conserved cysteine residues and a P1 lysine residue. Recombinant AvKTI, expressed in baculovirus-infected insect cells, showed a dual Inhibitory activity against trypsin (Ki 7.34 nM) and chymotrypsin (Ki 37.75 nM), defining a role for AvKTI as a spider-derived Kunitz-type Serine Protease Inhibitor. Additionally, AvKTI showed no detectable Inhibitory effects on factor Xa, thrombin, or tissue plasminogen activator; however, AvKTI inhibited plasmin (Ki 4.89 nM) and neutrophil elastase (Ki 169.07 nM), indicating that it acts as an antifibrinolytic factor and an antielastolytic factor. These findings constitute molecular evidence that AvKTI acts as a plasmin Inhibitor and an elastase Inhibitor and also provide a novel view of the functions of a spider-derived Kunitz-type Serine Protease Inhibitor.
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antifibrinolytic role of a bee venom Serine Protease Inhibitor that acts as a plasmin Inhibitor
PLOS ONE, 2012Co-Authors: Young Moo Choo, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Yuling Qiu, Mi Ri Sohn, Hung Dae Sohn, Byung Rae JinAbstract: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.
Hyung Joo Yoon - One of the best experts on this subject based on the ideXlab platform.
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antimicrobial activity of a honeybee apis cerana venom kazal type Serine Protease Inhibitor
Toxicon, 2013Co-Authors: Bo Yeon Kim, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Fengming Zou, Yongsoo Choi, Hyung Wook Kwon, Byung Rae JinAbstract:Insect-derived Kazal-type Serine Protease Inhibitors exhibit thrombin, elastase, plasmin, proteinase K, or subtilisin A inhibition activity, but so far, no functional roles for bee-derived Kazal-type Serine Protease Inhibitors have been identified. In this study, a bee (Apis cerana) venom Kazal-type Serine Protease Inhibitor (AcKTSPI) that acts as a microbial Serine Protease Inhibitor was identified. AcKTSPI contained a single Kazal domain that displayed six conserved cysteine residues and a P1 threonine residue. AcKTSPI was expressed in the venom gland and was present as a 10-kDa peptide in bee venom. Recombinant AcKTSPI Kazal domain (AcKTSPI-Kd) expressed in baculovirus-infected insect cells demonstrated Inhibitory activity against subtilisin A (Ki 67.03 nM) and proteinase K (Ki 91.53 nM), but not against α-chymotrypsin or trypsin, which implies a role for AcKTSPI as a microbial Serine Protease Inhibitor. However, AcKTSPI-Kd exhibited no detectable Inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or elastase. Additionally, AcKTSPI-Kd bound directly to Bacillus subtilis, Bacillus thuringiensis, Beauveria bassiana, and Fusarium graminearum but not to Escherichia coli. Consistent with these findings, AcKTSPI-Kd showed antibacterial activity against Gram-positive bacteria and antifungal activity against both plant-pathogenic and entomopathogenic fungi. These findings constitute molecular evidence that AcKTSPI acts as an Inhibitor of microbial Serine Proteases. This paper provides a novel view of the antimicrobial functions of a bee venom Kazal-type Serine Protease Inhibitor.
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A spider-derived Kunitz-type Serine Protease Inhibitor that acts as a plasmin Inhibitor and an elastase Inhibitor.
PLOS ONE, 2013Co-Authors: Hu Wan, Hyung Joo Yoon, Kwang Sik Lee, Bo Yeon Kim, Fengming Zou, Byung Rae JinAbstract:Kunitz-type Serine Protease Inhibitors are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis, and inflammation. While spider-derived Kunitz-type proteins show activity in trypsin or chymotrypsin inhibition and K+ channel blocking, no additional role for these proteins has been elucidated. In this study, we identified the first spider (Araneus ventricosus) Kunitz-type Serine Protease Inhibitor (AvKTI) that acts as a plasmin Inhibitor and an elastase Inhibitor. AvKTI possesses a Kunitz domain consisting of a 57-amino-acid mature peptide that displays features consistent with Kunitz-type Inhibitors, including six conserved cysteine residues and a P1 lysine residue. Recombinant AvKTI, expressed in baculovirus-infected insect cells, showed a dual Inhibitory activity against trypsin (Ki 7.34 nM) and chymotrypsin (Ki 37.75 nM), defining a role for AvKTI as a spider-derived Kunitz-type Serine Protease Inhibitor. Additionally, AvKTI showed no detectable Inhibitory effects on factor Xa, thrombin, or tissue plasminogen activator; however, AvKTI inhibited plasmin (Ki 4.89 nM) and neutrophil elastase (Ki 169.07 nM), indicating that it acts as an antifibrinolytic factor and an antielastolytic factor. These findings constitute molecular evidence that AvKTI acts as a plasmin Inhibitor and an elastase Inhibitor and also provide a novel view of the functions of a spider-derived Kunitz-type Serine Protease Inhibitor.
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antifibrinolytic role of a bee venom Serine Protease Inhibitor that acts as a plasmin Inhibitor
PLOS ONE, 2012Co-Authors: Young Moo Choo, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Yuling Qiu, Mi Ri Sohn, Hung Dae Sohn, Byung Rae JinAbstract: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.
Kwang Sik Lee - One of the best experts on this subject based on the ideXlab platform.
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antimicrobial activity of a honeybee apis cerana venom kazal type Serine Protease Inhibitor
Toxicon, 2013Co-Authors: Bo Yeon Kim, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Fengming Zou, Yongsoo Choi, Hyung Wook Kwon, Byung Rae JinAbstract:Insect-derived Kazal-type Serine Protease Inhibitors exhibit thrombin, elastase, plasmin, proteinase K, or subtilisin A inhibition activity, but so far, no functional roles for bee-derived Kazal-type Serine Protease Inhibitors have been identified. In this study, a bee (Apis cerana) venom Kazal-type Serine Protease Inhibitor (AcKTSPI) that acts as a microbial Serine Protease Inhibitor was identified. AcKTSPI contained a single Kazal domain that displayed six conserved cysteine residues and a P1 threonine residue. AcKTSPI was expressed in the venom gland and was present as a 10-kDa peptide in bee venom. Recombinant AcKTSPI Kazal domain (AcKTSPI-Kd) expressed in baculovirus-infected insect cells demonstrated Inhibitory activity against subtilisin A (Ki 67.03 nM) and proteinase K (Ki 91.53 nM), but not against α-chymotrypsin or trypsin, which implies a role for AcKTSPI as a microbial Serine Protease Inhibitor. However, AcKTSPI-Kd exhibited no detectable Inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or elastase. Additionally, AcKTSPI-Kd bound directly to Bacillus subtilis, Bacillus thuringiensis, Beauveria bassiana, and Fusarium graminearum but not to Escherichia coli. Consistent with these findings, AcKTSPI-Kd showed antibacterial activity against Gram-positive bacteria and antifungal activity against both plant-pathogenic and entomopathogenic fungi. These findings constitute molecular evidence that AcKTSPI acts as an Inhibitor of microbial Serine Proteases. This paper provides a novel view of the antimicrobial functions of a bee venom Kazal-type Serine Protease Inhibitor.
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A spider-derived Kunitz-type Serine Protease Inhibitor that acts as a plasmin Inhibitor and an elastase Inhibitor.
PLOS ONE, 2013Co-Authors: Hu Wan, Hyung Joo Yoon, Kwang Sik Lee, Bo Yeon Kim, Fengming Zou, Byung Rae JinAbstract:Kunitz-type Serine Protease Inhibitors are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis, and inflammation. While spider-derived Kunitz-type proteins show activity in trypsin or chymotrypsin inhibition and K+ channel blocking, no additional role for these proteins has been elucidated. In this study, we identified the first spider (Araneus ventricosus) Kunitz-type Serine Protease Inhibitor (AvKTI) that acts as a plasmin Inhibitor and an elastase Inhibitor. AvKTI possesses a Kunitz domain consisting of a 57-amino-acid mature peptide that displays features consistent with Kunitz-type Inhibitors, including six conserved cysteine residues and a P1 lysine residue. Recombinant AvKTI, expressed in baculovirus-infected insect cells, showed a dual Inhibitory activity against trypsin (Ki 7.34 nM) and chymotrypsin (Ki 37.75 nM), defining a role for AvKTI as a spider-derived Kunitz-type Serine Protease Inhibitor. Additionally, AvKTI showed no detectable Inhibitory effects on factor Xa, thrombin, or tissue plasminogen activator; however, AvKTI inhibited plasmin (Ki 4.89 nM) and neutrophil elastase (Ki 169.07 nM), indicating that it acts as an antifibrinolytic factor and an antielastolytic factor. These findings constitute molecular evidence that AvKTI acts as a plasmin Inhibitor and an elastase Inhibitor and also provide a novel view of the functions of a spider-derived Kunitz-type Serine Protease Inhibitor.
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antifibrinolytic role of a bee venom Serine Protease Inhibitor that acts as a plasmin Inhibitor
PLOS ONE, 2012Co-Authors: Young Moo Choo, Hyung Joo Yoon, Hu Wan, Kwang Sik Lee, Yuling Qiu, Mi Ri Sohn, Hung Dae Sohn, Byung Rae JinAbstract: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.
