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(1 - 5 of 5)
- Title
- Kallikreins are Associated with Secondary Progressive Multiple Sclerosis and Promote Neurodegeneration.
- Creator
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Scarisbrick, Isobel, Linbo, Rachel, Vandell, Alexander, Keegan, Mark, Blaber, Sachiko, Blaber, Michael, Sneve, Diane, Lucchinetti, Claudia F., Rodriguez, Moses, Diamandis,...
Show moreScarisbrick, Isobel, Linbo, Rachel, Vandell, Alexander, Keegan, Mark, Blaber, Sachiko, Blaber, Michael, Sneve, Diane, Lucchinetti, Claudia F., Rodriguez, Moses, Diamandis, Eleftherios P.
Show less - Abstract/Description
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Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores...
Show moreTissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p
Show less - Date Issued
- 2008
- Identifier
- FSU_migr_biomed_faculty_publications-0008
- Format
- Citation
- Title
- A Completed KLK Activome Profile: Investigation of Activation Profiles of KLK9, 10, and 15..
- Creator
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Yoon, Hyesook, Blaber, Sachiko, Debela, Mekdes, Goettig, Peter, Scarisbrick, Isobel, Blaber, Michael
- Abstract/Description
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We previously reported the activation profiles of the human kallikrein-related peptidases (KLKs) as determined from a KLK pro-peptide fusion-protein system. That report described the activity profiles of 12 of the 15 mature KLKs versus the 15 different pro-KLK sequences. The missing profiles in the prior report, involving KLK9, 10, and 15, are now described. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mass spectrometry, and N-terminal sequence analyses show that KLK9 and 10...
Show moreWe previously reported the activation profiles of the human kallikrein-related peptidases (KLKs) as determined from a KLK pro-peptide fusion-protein system. That report described the activity profiles of 12 of the 15 mature KLKs versus the 15 different pro-KLK sequences. The missing profiles in the prior report, involving KLK9, 10, and 15, are now described. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mass spectrometry, and N-terminal sequence analyses show that KLK9 and 10 exhibit low hydrolytic activities towards all of the 15 pro-KLK sequences, while KLK15 exhibits significant activity towards both Arg- and Lys-containing KLK pro-sequences. The ability of KLK15 to activate pro-KLK8, 12, and 14 is confirmed using recombinant pro-KLK proteins, and shown to be significant for activation of pro-KLK8 and 14, but not 12. These additional data for KLK9, 10, and 15 now permit a completed KLK activome profile, using a KLK pro-peptide fusion-protein system, to be described. The results suggest that KLK15, once activated, can potentially feed back into additional pro-KLK activation pathways. Conversely, KLK9 and 10, once activated, are unlikely to participate in further pro-KLK activation pathways, although similar to KLK1 they may activate other bioactive peptides.
Show less - Date Issued
- 2009
- Identifier
- FSU_migr_biomed_faculty_publications-0012
- Format
- Citation
- Title
- Functional Intersection of the Kallikrein-Related Peptidases (KLKs) and Thrombostasis Axis.
- Creator
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Blaber, Michael, Yoon, Hyesook, Juliano, Maria, Scarisbrick, Isobel, Blaber, Sachiko
- Abstract/Description
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A large body of emerging evidence indicates a functional interaction between the kallikrein-related peptidases (KLKs) and proteases of the thrombostasis axis. These interactions appear relevant for both normal health as well as pathologies associated with inflammation, tissue injury, and remodeling. Regulatory interactions between the KLKs and thrombostasis proteases could impact several serious human diseases, including neurodegeneration and cancer. The emerging network of specific...
Show moreA large body of emerging evidence indicates a functional interaction between the kallikrein-related peptidases (KLKs) and proteases of the thrombostasis axis. These interactions appear relevant for both normal health as well as pathologies associated with inflammation, tissue injury, and remodeling. Regulatory interactions between the KLKs and thrombostasis proteases could impact several serious human diseases, including neurodegeneration and cancer. The emerging network of specific interactions between these two protease families appears to be complex, and much work remains to elucidate it. Complete understanding how this functional network resolves over time, given specific initial conditions, and how it might be controllably manipulated, will probably contribute to the emergence of novel diagnostics and therapeutic agents for major diseases.
Show less - Date Issued
- 2010
- Identifier
- FSU_migr_biomed_faculty_publications-0018, 10.1515/BC.2010.024, PMC3047482
- Format
- Citation
- Title
- Kallikrein 6 is a Novel Molecular Trigger of Reactive Astrogliosis.
- Creator
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Scarisbrick, Isobel, Radulovic, Maja, Burda, Joshua, Larson, Nadya, Blaber, Sachiko, Giannini, Caterina, Blaber, Michael, Vandell, Alexander
- Abstract/Description
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Kallikrein-related peptidase 6 (KLK6) is a trypsin-like serine protease upregulated at sites of central nervous system (CNS) injury, including de novo expression by reactive astrocytes, yet its physiological actions are largely undefined. Taken with recent evidence that KLK6 activates G-protein-coupled protease-activated receptors (PARs), we hypothesized that injury-induced elevations in KLK6 contribute to the development of astrogliosis and that this occurs in a PAR-dependent fashion. Using...
Show moreKallikrein-related peptidase 6 (KLK6) is a trypsin-like serine protease upregulated at sites of central nervous system (CNS) injury, including de novo expression by reactive astrocytes, yet its physiological actions are largely undefined. Taken with recent evidence that KLK6 activates G-protein-coupled protease-activated receptors (PARs), we hypothesized that injury-induced elevations in KLK6 contribute to the development of astrogliosis and that this occurs in a PAR-dependent fashion. Using primary murine astrocytes and the Neu7 astrocyte cell line, we show that KLK6 causes astrocytes to transform from an epitheliod to a stellate morphology and to secrete interleukin 6 (IL-6). By contrast, KLK6 reduced expression of glial fibrillary acidic protein (GFAP). The stellation-promoting activities of KLK6 were shown to be dependent on activation of the thrombin receptor, PAR1, as a PAR1-specific inhibitor, SCH79797, blocked KLK6-induced morphological changes. The ability of KLK6 to promote astrocyte stellation was also shown to be linked to activation of protein kinase C (PKC). These studies indicate that KLK6 is positioned to serve as a molecular trigger of select physiological processes involved in the development of astrogliosis and that this is likely to occur at least in part by activation of the G-protein-coupled receptor, PAR1.
Show less - Date Issued
- 2012
- Identifier
- FSU_migr_biomed_faculty_publications-0030, 10.1515/hsz-2011-0241
- Format
- Citation
- Title
- Activation Profiles of Human Kallikrein-Related Peptidases by Matrix Metalloproteinases.
- Creator
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Yoon, Hyesook, Blaber, Sachiko, Li, Wu, Scarisbrick, Isobel, Blaber, Michael
- Abstract/Description
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Abstract The 15 human kallikrein-related peptidases (KLKs) are clinically important biomarkers and therapeutic targets of interest in inflammation, cancer, and neurodegenerative disease. KLKs are secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their amino-terminal pro-peptide, and this is a key step in their functional regulation. Physiologically relevant KLK regulatory cascades of activation have been described in skin...
Show moreAbstract The 15 human kallikrein-related peptidases (KLKs) are clinically important biomarkers and therapeutic targets of interest in inflammation, cancer, and neurodegenerative disease. KLKs are secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their amino-terminal pro-peptide, and this is a key step in their functional regulation. Physiologically relevant KLK regulatory cascades of activation have been described in skin desquamation and semen liquefaction, and work by a large number of investigators has elucidated pairwise and autolytic activation relationships among the KLKs with the potential for more extensive activation cascades. More recent work has asked whether functional intersection of KLKs with other types of regulatory proteases exists. Such studies show a capacity for members of the thrombostasis axis to act as broad activators of pro-KLKs. In the present report, we ask whether such functional intersection is possible between the KLKs and the members of the matrix metalloproteinase (MMP) family by evaluating the ability of the MMPs to activate pro-KLKs. The results identify MMP-20 as a broad activator of pro-KLKs, suggesting the potential for intersection of the KLK and MMP axes under pathological dysregulation of MMP-20 expression.
Show less - Date Issued
- 2013
- Identifier
- FSU_migr_biomed_faculty_publications-0042, 10.1515/hsz-2012-0249, PMC3709557
- Format
- Citation
