Findings from Children's Hospital in the Area of Cysteine Endopeptidases Reported (Real-Time Detection of CTL Function Reveals Distinct Patterns of Caspase Activation Mediated by Fas versus Granzyme B)
By a News Reporter-Staff News Editor at Biotech Week -- Current study results on Enzymes and Coenzymes have been published. According to news reporting from Cincinnati, Ohio, by NewsRx journalists, research stated, "Activation of caspase-mediated apoptosis is reported to be a hallmark of both granzyme B- and Fas-mediated pathways of killing by CTLs; however, the kinetics of caspase activation remain undefined owing to an inability to monitor target cell-specific apoptosis in real time. We have overcome this limitation by developing a novel biosensor assay that detects continuous, protease- specific activity in target cells."
The news correspondents obtained a quote from the research from Children's Hospital, "Biosensors were engineered from a circularly permuted luciferase, linked internally by either caspase 3/7 or granzyme B/caspase 8 cleavage sites, thus allowing activation upon proteolytic cleavage by the respective proteases. Coincubation of murine CTLs with target cells expressing either type of biosensor led to a robust luminescent signal within minutes of cell contact. The signal was modulated by the strength of TCR signaling, the ratio of CTL/target cells, and the type of biosensor used. Additionally, the luciferase signal at 30 min correlated with target cell death, as measured by a Cr-51-release assay. The rate of caspase 3/7 biosensor activation was unexpectedly rapid following granzyme B- compared with Fas-mediated signal induction in murine CTLs; the latter appeared gradually after a 90-min delay in perforin- or granzyme B-deficient CTLs. Remarkably, the Fas-dependent, caspase 3/7 biosensor signal induced by perforin-deficient human CTLs was also detectable after a 90-min delay when measured by redirected killing."
According to the news reporters, the research concluded: "Thus, we have used a novel, real-time assay to demonstrate the distinct pattern of caspase activation induced by granzyme B versus Fas in human and murine CTLs."
For more information on this research see: Real-Time Detection of CTL Function Reveals Distinct Patterns of Caspase Activation Mediated by Fas versus Granzyme B. Journal of Immunology, 2014;193(2):519-528. Journal of Immunology can be contacted at: Amer Assoc Immunologists, 9650 Rockville Pike, Bethesda, MD 20814, USA. (The American Association of Immunologists - www.aai.org; Journal of Immunology - www.jimmunol.org)
Our news journalists report that additional information may be obtained by contacting J.Z. Li, Cincinnati Children's Hospital, Div Immunobiol, Cincinnati, OH 45229, United States. Additional authors for this research include S.K. Figueira, A.C.A. Vrazo, B.F. Binkowski, B.L. Butler, Y. Tabata, A. Filipovich, M.B. Jordan and K.A. Risma (see also Enzymes and Coenzymes).
Keywords for this news article include: Ohio, Granzymes, Cincinnati, Biosensing, Luciferases, United States, Bioengineering, Bionanotechnology, Effector Caspases, Nanobiotechnology, Peptide Hydrolases, Enzymes and Coenzymes, Serine Endopeptidases, Cysteine Endopeptidases, North and Central America, Apoptosis Regulatory Proteins
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