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(1 - 4 of 4)
- Title
- Functional Role of Kallikrein 6 in Regulating Immune Cell Survival.
- Creator
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Scarisbrick, Isobel, Epstein, Benjamin, Cloud, Beth, Yoon, Hyesook, Wu, Jianmin, Renner, Danielle, Blaber, Sachiko, Blaber, Michael, Vandell, Alexander, Bryson, Alexandra
- Abstract/Description
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BACKGROUND: Kallikrein 6 (KLK6) is a newly identified member of the kallikrein family of secreted serine proteases that prior studies indicate is elevated at sites of central nervous system (CNS) inflammation and which shows regulated expression with T cell activation. Notably, KLK6 is also elevated in the serum of multiple sclerosis (MS) patients however its potential roles in immune function are unknown. Herein we specifically examine whether KLK6 alters immune cell survival and the...
Show moreBACKGROUND: Kallikrein 6 (KLK6) is a newly identified member of the kallikrein family of secreted serine proteases that prior studies indicate is elevated at sites of central nervous system (CNS) inflammation and which shows regulated expression with T cell activation. Notably, KLK6 is also elevated in the serum of multiple sclerosis (MS) patients however its potential roles in immune function are unknown. Herein we specifically examine whether KLK6 alters immune cell survival and the possible mechanism by which this may occur. METHODOLOGY/PRINCIPAL FINDINGS: Using murine whole splenocyte preparations and the human Jurkat T cell line we demonstrate that KLK6 robustly supports cell survival across a range of cell death paradigms. Recombinant KLK6 was shown to significantly reduce cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Moreover, KLK6-over expression in Jurkat T cells was shown to generate parallel pro-survival effects. In mixed splenocyte populations the vigorous immune cell survival promoting effects of KLK6 were shown to include both T and B lymphocytes, to occur with as little as 5 minutes of treatment, and to involve up regulation of the pro-survival protein B-cell lymphoma-extra large (Bcl-XL), and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim). The ability of KLK6 to promote survival of splenic T cells was also shown to be absent in cell preparations derived from PAR1 deficient mice. CONCLUSION/SIGNIFICANCE: KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of PAR1. These findings point to a novel molecular mechanism regulating lymphocyte survival that is likely to have relevance to a range of immunological responses that depend on apoptosis for immune clearance and maintenance of homeostasis.
Show less - Date Issued
- 2011
- Identifier
- FSU_migr_biomed_faculty_publications-0022, 10.1371/journal.pone.0018376
- Format
- Citation
- Title
- Personality, Metabolic Rate and Aerobic Capacity.
- Creator
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Terracciano, Antonio, Schrack, Jennifer, Sutin, Angelina, Chan, Wayne, Simonsick, Eleanor M., Ferrucci, Luigi
- Abstract/Description
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Personality traits and cardiorespiratory fitness in older adults are reliable predictors of health and longevity. We examined the association between personality traits and energy expenditure at rest (basal metabolic rate) and during normal and maximal sustained walking. Personality traits and oxygen (VO(2)) consumption were assessed in 642 participants from the Baltimore Longitudinal Study of Aging. Results indicate that personality traits were mostly unrelated to resting metabolic rate and...
Show morePersonality traits and cardiorespiratory fitness in older adults are reliable predictors of health and longevity. We examined the association between personality traits and energy expenditure at rest (basal metabolic rate) and during normal and maximal sustained walking. Personality traits and oxygen (VO(2)) consumption were assessed in 642 participants from the Baltimore Longitudinal Study of Aging. Results indicate that personality traits were mostly unrelated to resting metabolic rate and energy expenditure at normal walking pace. However, those who scored lower on neuroticism (r = -0.12) and higher on extraversion (r = 0.11), openness (r = 0.13), and conscientiousness (r = 0.09) had significantly higher energy expenditure at peak walking pace. In addition to greater aerobic capacity, individuals with a more resilient personality profile walked faster and were more efficient in that they required less energy per meter walked. The associations between personality and energy expenditure were not moderated by age or sex, but were in part explained by the proportion of fat mass. In conclusion, differences in personality may matter the most during more challenging activities that require cardiorespiratory fitness. These findings suggest potential pathways that link personality to health outcomes, such as obesity and longevity.
Show less - Date Issued
- 2013
- Identifier
- FSU_migr_mhs-0011, 10.1371/journal.pone.0054746
- Format
- Citation
- Title
- Pharmacokinetic Properties of 2(nd)-Generation Fibroblast Growth Factor-1 Mutants for Therapeutic Application.
- Creator
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Xia, Xue, Babcock, Joseph, Blaber, Sachiko, Harper, Kathleen, Blaber, Michael
- Abstract/Description
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Fibroblast growth factor-1 (FGF-1) is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for...
Show moreFibroblast growth factor-1 (FGF-1) is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for therapeutic use. We report a pharmacokinetic (PK) study in rabbits of human FGF-1 in the presence and absence of heparin, as well as three mutant forms having differential effects upon thermostability, buried reactive thiols, and heparin affinity. The results support the hypothesis that heparan sulfate proteoglycan (HSPG) in the vasculature of liver, kidney and spleen serves as the principle peripheral compartment in the distribution kinetics. The addition of heparin to FGF-1 is shown to increase endocrine-like properties of distribution. Mutant forms of FGF-1 that enhance thermostability or eliminate buried reactive thiols demonstrate a shorter distribution half-life, a longer elimination half-life, and a longer mean residence time (MRT) in comparison to wild-type FGF-1. The results show how such mutations can produce useful 2nd-generation forms with tailored PK profiles for specific therapeutic application.
Show less - Date Issued
- 2012
- Identifier
- FSU_migr_biomed_faculty_publications-0041, 10.1371/journal.pone.0048210
- Format
- Citation
- Title
- δ/ω-Plectoxin-Pt1a: An Excitatory Spider Toxin with Actions on both Ca(2+) and Na(+) Channels.
- Creator
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Zhou, Yi, Zhao, Mingli, Fields, Gregg B., Wu, Chun-Fang, Branton, W.
- Abstract/Description
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The venom of spider Plectreurys tristis contains a variety of peptide toxins that selectively target neuronal ion channels. O-palmitoylation of a threonine or serine residue, along with a characteristic and highly constrained disulfide bond structure, are hallmarks of a family of toxins found in this venom. Here, we report the isolation and characterization of a new toxin, δ/ω-plectoxin-Pt1a, from this spider venom. It is a 40 amino acid peptide containing an O-palmitoylated Ser-39. Analysis...
Show moreThe venom of spider Plectreurys tristis contains a variety of peptide toxins that selectively target neuronal ion channels. O-palmitoylation of a threonine or serine residue, along with a characteristic and highly constrained disulfide bond structure, are hallmarks of a family of toxins found in this venom. Here, we report the isolation and characterization of a new toxin, δ/ω-plectoxin-Pt1a, from this spider venom. It is a 40 amino acid peptide containing an O-palmitoylated Ser-39. Analysis of δ/ω-plectoxin-Pt1a cDNA reveals a small precursor containing a secretion signal sequence, a 14 amino acid N-terminal propeptide, and a C-terminal amidation signal. The biological activity of δ/ω-plectoxin-Pt1a is also unique. It preferentially blocks a subset of Ca(2+) channels that is apparently not required for neurotransmitter release; decreases threshold for Na(+) channel activation; and slows Na(+) channel inactivation. As δ/ω-plectoxin-Pt1a enhances synaptic transmission by prolonging presynaptic release of neurotransmitter, its effects on Na(+) and Ca(2+) channels may act synergistically to sustain the terminal excitability.
Show less - Date Issued
- 2013
- Identifier
- FSU_migr_biomed_faculty_publications-0044
- Format
- Citation
