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3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide + H2O
?
Abz-GLFRSLSS(K-dnp)D + H2O
Abz-GLFR + SLSS(K-dnp)D
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a quenched fluorescence peptide substrate
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-
?
Abz-VANRSAS(Kdnp)D + H2O
Abz-VANR + SAS(Kdnp)D
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a quenched fluorescence peptide substrate
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-
?
Benzyloxycarbonyl-Arg thiobenzyl ester + H2O
?
benzyloxycarbonyl-Gly-Arg thiobenzyl ester + H2O
benzyloxycarbonyl-Gly-Arg + phenylmethanethiol
benzyloxycarbonyl-Lys-thiobenzyl ester + H2O
benzyloxycarbonyl-Lys + phenylmethanethiol
Boc-Ala-Ala-Arg-SBzl + H2O
?
Boc-Trp-Arg-SBzl + H2O
?
-
thioester substrate, recombinant granzyme A
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?
CBZ-Lys-SBzl + H2O
?
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thioester substrate, recombinant granzyme A
-
?
D-(epsilon-Benzyloxycarbonyl)Lys-Pro-Arg 4-methylcoumarin 7-amide + H2O
?
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-
-
-
?
D-Pro-Phe-Arg 4-nitroanilide + H2O
D-Pro-Phe-Arg + 4-nitroaniline
Gly-Pro-Arg 4-methylcoumarin 7-amide + H2O
?
-
-
-
-
?
H-D-Pro-Phe-Arg p-nitroanilide + H2O
H-D-Pro-Phe-Arg + p-nitroaniline
i.e. S2302, measurement of enzymatic activity of granzyme A activity in lysates of CD8+ TAL
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-
?
Ku70 double strand break repair protein + H2O
?
-
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cleavage of Ku70 after R301, disrupting Ku complex binding to DNA and blocking of Ku70 antiapoptotic functions, cleavage of Ku70 after R301, disrupting Ku complex binding to DNA
-
?
N-acetyl-Ile-Glu-Pro-Asp p-nitroanilide + H2O
N-acetyl-Ile-Glu-Pro-Asp + p-nitroaniline
measurement of enzymatic activity of granzyme A activity in lysates of CD8+ TAL
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-
?
N-alpha-benzyloxycarbonyl-Arg-SBzl + H2O
?
NADH dehydrogenase (ubiquinone) Fe-S protein 3 + H2O
?
-
-
-
?
Nalpha-benzyloxycarbonyl-Lys-SBzl + H2O
Nalpha-benzyloxycarbonyl-Lys + phenylmethanethiol
-
-
-
?
Precursor of interleukin-1beta + H2O
Interleucin-1beta
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i.e. pIL-1beta, cleavage at Arg120
-
?
Pro-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
PSSCL + H2O
Pro-Ser + Ser-Lys-Lys
-
-
-
?
Suc-AAPR-p-nitroanilide + H2O
?
-
-
-
-
?
Tosyl-Gly-Pro-Arg 4-nitroanilide + H2O
?
-
-
-
-
?
Val-Pro-Arg 4-methylcoumarin 7-amide + H2O
?
additional information
?
-
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide + H2O
?
MTT, benzyloxy-carbonyl-Lys-thiobenzyl ester, standard MTT-assay measuring loss of mitochondrial respiration, interspecies differences of granzyme A between human and mouse analyzed, different cytotoxic potential identified
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-
?
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide + H2O
?
MTT, benzyloxy-carbonyl-Lys-thiobenzyl ester, standard MTT-assay measuring loss of mitochondrial respiration, interspecies differences of granzyme A between human and mouse analyzed, mouse granzyme A is considerably more cytotoxic than human granzyme A
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-
?
Benzyloxycarbonyl-Arg thiobenzyl ester + H2O
?
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-
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-
?
Benzyloxycarbonyl-Arg thiobenzyl ester + H2O
?
-
-
-
-
?
benzyloxycarbonyl-Gly-Arg thiobenzyl ester + H2O
benzyloxycarbonyl-Gly-Arg + phenylmethanethiol
-
-
-
-
?
benzyloxycarbonyl-Gly-Arg thiobenzyl ester + H2O
benzyloxycarbonyl-Gly-Arg + phenylmethanethiol
-
-
-
-
?
benzyloxycarbonyl-Lys-thiobenzyl ester + H2O
benzyloxycarbonyl-Lys + phenylmethanethiol
-
-
-
-
?
benzyloxycarbonyl-Lys-thiobenzyl ester + H2O
benzyloxycarbonyl-Lys + phenylmethanethiol
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-
-
-
?
Boc-Ala-Ala-Arg-SBzl + H2O
?
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thioester substrate, recombinant granzyme A
-
?
Boc-Ala-Ala-Arg-SBzl + H2O
?
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-
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-
?
D-Pro-Phe-Arg 4-nitroanilide + H2O
D-Pro-Phe-Arg + 4-nitroaniline
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-
-
-
?
D-Pro-Phe-Arg 4-nitroanilide + H2O
D-Pro-Phe-Arg + 4-nitroaniline
-
low or no activity against peptide synthetic substrates carrying other amino acid sequences at position P2, P3 adjacent to L-arginine or against substrates in which amino acids other than L-arginine are bound to the nitroanilide group
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?
histone H4 + H2O
?
histone H4 is a substrate for GzmA in staurosporine-induced cells
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?
histone H4 + H2O
?
the histone H4 N-terminal tail is cleaved by GzmA, the enzyme cleaves only deacetylated histone H4
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?
N-alpha-benzyloxycarbonyl-Arg-SBzl + H2O
?
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?
N-alpha-benzyloxycarbonyl-Arg-SBzl + H2O
?
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thioester substrate, recombinant granzyme A
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?
PHAPII + H2O
?
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?
PHAPII + H2O
?
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HLA-associated protein, cleaved by the recombinant enzyme at nanomolar concentrations
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?
Pro-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
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?
Pro-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
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?
protein NDUFS3 + H2O
?
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GzmA cleavage of native Ndufs3 disrupts complex I electron transport
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-
?
protein NDUFS3 + H2O
?
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GzmA accesses the mitochondrial matrix to cleave the complex I protein NDUFS3, an iron-sulfur subunit of the NADH:ubiquinone oxidoreductase complex I, after Lys56 to interfere with NADH oxidation and generate superoxide anions. NDUFS3 is cleaved in cells treated with GzmA and perforin in a dose-dependent manner. Human GzmA cleaves both human and mouse NDUFS3. GzmA induces caspase-independent increased reactive oxygen species
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?
Val-Pro-Arg 4-methylcoumarin 7-amide + H2O
?
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?
Val-Pro-Arg 4-methylcoumarin 7-amide + H2O
?
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?
additional information
?
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the enzyme may function as a common component necessary for lysis of target cells by cytotoxic T-lymphocytes and natural killer cells
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?
additional information
?
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overview: possible roles of granzyme A: 1. involvement in T or NK cell-mediated cytolysis, 2. in extravasation of T-lymphocytes, 3. in regulation of B cell growth, 4. in control of viral infection
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?
additional information
?
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cell death-inducing serine protease
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?
additional information
?
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most abundant protease in cytotoxic T lymphocytes, granzyme A pathway of cell-mediated cytotoxicity, produced as proenzyme, activated by the dipetidyl exopeptidase cathepsin C
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?
additional information
?
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most abundant protease in cytotoxic T lymphocytes, granzyme A pathway of cell-mediated cytotoxicity, produced as proenzyme, activated by the dipetidyl exopeptidase cathepsin C
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?
additional information
?
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compared with granzyme B, granzyme A is minor effector of target cell lysis by natural killer cells
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?
additional information
?
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extracellular enzyme is delivered to the cytosol by perforin, where it causes a rapid increase in reactive oxygen species and mitochondrial transmembrane potential loss, but does not cleave bid or cause apoptotic factor release. Mitochondrial effect is direct, does not require cytosol, and is insensitive to bcl-2 and caspase inhibition. Mitochondrial damage is an essential first step in killer cell granule-mediated pathways of apoptosis
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?
additional information
?
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extracellular substrates of granzyme A and proposed functions summarized, pathological consequences of extracellular granzyme A in disease reviewed, role of anionic interactions in extracellular substrate binding summarized, evidence for the role of glycosaminoglycan-binding sites of granzyme A in extracellular matrix remodelling described
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?
additional information
?
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interspecies differences of granzyme A between human and mouse analyzed by 51Cr-release assay, different cytotoxic potential identified
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?
additional information
?
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interspecies differences of granzyme A between human and mouse analyzed by 51Cr-release assay, different cytotoxic potential identified
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?
additional information
?
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studies on sensitivity to granzyme A-mediated cell death in chilblain lupus patients, less sensitivity to granzyme A-mediated apoptosis in cells carrrying the heterozygous missense mutation D18N in the 3'-5' DNA repair exonuclease TREX1
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?
additional information
?
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study to analyze importance of granzyme A in development of chronic obstructive pulmonary disease (COPD)
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?
additional information
?
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study to analyze importance of granzyme A in development of chronic obstructive pulmonary disease (COPD)
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?
additional information
?
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study to analyze the role of granzyme A in development of chronic obstructive pulmonary disease (COPD)
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?
additional information
?
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study to analyze the role of granzyme A in development of chronic obstructive pulmonary disease (COPD)
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?
additional information
?
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characterization of substrate specificity using an N-terminal peptide-centric proteomics technology. Among 260 cleavage sites, a basic residue at P1 position is favored, and P1 arginine is preferred over lysine. P4 shows a preference for Pro, Ala and Val. In P1' position, long linear amino acids with significant hydrophobic character are enriched. Gly is highly favored at P2' position. The substrate repertoires of granzyme A and granzyme B are partially overlapping
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?
additional information
?
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substrate specifiicty, comparison to the murine enzyme at the peptide and proteome-wide levels, overview
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?
additional information
?
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substrate specifiicty, comparison to the murine enzyme at the peptide and proteome-wide levels, overview
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?
additional information
?
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TSP-1 has the capacity to stimulate B lymphocytes for proliferation in the absence of antigen
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?
additional information
?
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overview: possible roles of granzyme A: 1. involvement in T or NK cell-mediated cytolysis, 2. in extravasation of T-lymphocytes, 3. in regulation of B cell growth, 4. in control of viral infection
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?
additional information
?
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by cleaving a variety of basement membrane-associated substrates, granzyme A may disintegrate the supramolecular structure of subendothelial basement membranes in a way that allows a more rapid emigration of activated T-cells
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?
additional information
?
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substrate specificity, comparison to the human enzyme at the peptide and proteome-wide levels, overview
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?
additional information
?
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involvement of granzyme A in exacerbation and perpetuation of enteritis indicated, early increase of granzyme A in rats with experimentally induced ulcerative colitis shown
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?
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additional information
ability of human and mouse granzyme A to kill human or mouse cells in the presence of perforin analyzed by standard MTT-assay and by 51Cr-release assay, recombinant and native proteins tested, cytotoxic potential between mouse and human granzyme A different
additional information
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ability of human and mouse granzyme A to kill human or mouse cells in the presence of perforin analyzed by standard MTT-assay and by 51Cr-release assay, recombinant and native proteins tested, cytotoxic potential between mouse and human granzyme A different
additional information
ability of human and mouse granzyme A to kill human or mouse cells in the presence of perforin analyzed, recombinant and native proteins tested, cytotoxic potential between mouse and human granzyme A different
additional information
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ability of human and mouse granzyme A to kill human or mouse cells in the presence of perforin analyzed, recombinant and native proteins tested, cytotoxic potential between mouse and human granzyme A different
additional information
constitutive expression in human PMNs shown by flow cytometry, Western blot, enzyme-linked immunosorbent assay and quantitative RT-PCR, up-regulation upon PMN stimulation shown
additional information
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constitutive expression in human PMNs shown by flow cytometry, Western blot, enzyme-linked immunosorbent assay and quantitative RT-PCR, up-regulation upon PMN stimulation shown
additional information
detection of extracellular granzyme A during disease reviewed, elevated levels during viral and bacterial infection, arthritis and other diseases
additional information
expression shown by flow cytometry, Western blot, enzyme-linked immunosorbent assay and quantitative RT-PCR, up-regulation of expression upon stimulation shown
additional information
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expression shown by flow cytometry, Western blot, enzyme-linked immunosorbent assay and quantitative RT-PCR, up-regulation of expression upon stimulation shown
additional information
expression shown by flow cytometry, Western blot, enzyme-linked immunosorbent assay and quantitative RT-PCR, up-regulation upon stimulation shown
additional information
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expression shown by flow cytometry, Western blot, enzyme-linked immunosorbent assay and quantitative RT-PCR, up-regulation upon stimulation shown
additional information
glucocorticoid sensitivity among cell lines derived from acute lymphoblastic leukemia patients analyzed, correlation between glucocorticoid-induced apoptosis and glucocorticoid-induced mRNA expression of granzyme A shown
additional information
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glucocorticoid sensitivity among cell lines derived from acute lymphoblastic leukemia patients analyzed, correlation between glucocorticoid-induced apoptosis and glucocorticoid-induced mRNA expression of granzyme A shown
additional information
RNA accumulation and immunohistochemistry of granzyme A investigated
additional information
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RNA accumulation and immunohistochemistry of granzyme A investigated
additional information
RNA accumulation and immunohistochemistry of granzyme A investigated, application of Laser capture dissection (LCM) to analyse accumulation of granzyme A in specific lung tissue
additional information
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RNA accumulation and immunohistochemistry of granzyme A investigated, application of Laser capture dissection (LCM) to analyse accumulation of granzyme A in specific lung tissue
additional information
studies on a corelation between the heterozygous missense mutation D18N in the 3'-5' DNA repair exonuclease TREX1 and the autoimmune disease chilblain lupus, granzyme A-mediated cytotoxicity assay described, less sensitivity to granzyme A-mediated cell death in cells carrying the D18N mutation of the 3'-5' DNA repair exonuclease TREX1 identified, association between loss of TREX1 enzyme activity and impaired granzyme A-mediated apoptosis demonstrated
additional information
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additional information
ability of human and mouse granzyme A to kill human or mouse cells in the presence of perforin analyzed, recombinant and native proteins tested, cytotoxic potential between mouse and human granzyme A different, mouse but not human granzyme A induces perforin-dependent cell death
additional information
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ability of human and mouse granzyme A to kill human or mouse cells in the presence of perforin analyzed, recombinant and native proteins tested, cytotoxic potential between mouse and human granzyme A different, mouse but not human granzyme A induces perforin-dependent cell death
additional information
enzymatic activity of granzyme A measured in lysates of CD8+ tumor associated lymphocytes of interleukin 4-deficient and wild-type BALB/c mice, significant increase in the fraction of CD8+ tumor associated T-cells expressing granzyme A identified, in interleukin 4-deficient mice, the frequency of CD8+ tumor associated lymphocytes expressing granzyme A significantly increases between days 8 and 14, expression at background levels by day 21, increase in the percentage of CD8+ tumor associated lymphocytes expressing granzyme A less pronounced in wild-type mice
additional information
measurement of granzyme A activity in large intestinal mucosal extracts of rats described
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acute lymphoblastic leukemia-derived cell line 697 used as a positive control, granzyme A mediated glucocorticoid-induced apoptosis shown
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primary type II pneumocytes and type II pneumocyte, from patients with chronic obstructive pulmonary disease, enriched by Laser capture microdissection (LCM)
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peripheral lung tissue from patients with chronic obstructive pulmonary disease, enriched by Laser capture microdissection (LCM)
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medium expression
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predominant expression
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predominant expression
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51Cr-release assay applied
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no expression of granzyme A in promyelocytic cell line HL-60 identified
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medium expression
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standard MTT-assay applied
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medium expression
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whole-blood leucocyte preparation discriminating between the distinct subpopulations, expression in CD8+ CTLs and in CD56+ NK cells shown
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less sensitivity to granzyme A-mediated cell death in lymphoblastoid cells carrying the D18N mutation in the 3'-5' DNA repair exonuclease TREX1 identified
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standard MTT-assay applied
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low expression
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PBMCs, expression in
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PMNs, polymorphonuclear neutrophils, expression in CD15+ population identified, differentiated cell stage, phagocytic stimuli of PMNs increase expression
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predominant expression
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BALF, from community-acquired pneumonia (CAP) patients from the Streptococcus pneumoniae serotype 3-infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels are increased in BALF obtained from the infected lung, expression analysis, overview
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BALF
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BALF
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constitutive expression of granzyme A
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constitutive expression of granzyme A
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constitutive expression of granzyme A
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large intestinal mucosa of rats with experimentally induced ulcerative colitis
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low expression
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human lungs show constitutive GzmA expression by both parenchymal and nonparenchymal cells
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GZMA is expressed in lungs from wild-type and Mycobacterium tuberculosis-infected mice
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GZMA is expressed in lungs from wild-type and Mycobacterium tuberculosis-infected mice
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cytotoxic lymphocyte subsets and T regulatory cells, most circulating CD56+8- NK cells and half of circulating CD8+ T lymphocytes coexpress both granzymes A and B. Activation of CD8+ T-lymphocytes with concanavalin A and of CD4+ T-lymphocytes with antibodies to CD3/CD28 or CD3/CD46 induces substantial expression of granzyme B, but not of granzyme A
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peripheral blood lymphocytes, similar distribution of enzyme, granzyme M and perforin. Expression in almost all CD16+CD56+ NK cells, CD3+CD56+ NKT cells and gammadelta T cells as well in 20-30% of all CD3+CD8+ Tc cells
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lysates of CD8+ tumor associated lymphocytes, Interleukin 4-deficient mice
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CD57+ natural killer cells
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constitutive expression of granzyme A
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constitutive expression of granzyme A
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constitutive expression of granzyme A
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low expression
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predominant expression
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cee lysates, activated, including normal peripheral blood lymphocytes previously sensitized by interleukin 2 or nitrogen, not expressed by resting T-lymphocytes
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cytotoxic
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rectal CD8+ T cell
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CD8+ cytotoxic T lymphocytes
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CD8+ cell
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cee lysates, activated, including normal peripheral blood lymphocytes previously sensitized by interleukin 2 or nitrogen, not expressed by resting T-lymphocytes
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cytotoxic
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CD8+ and CD4+ cells
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regulatory T cells (Tregs), CD4+ T-cells and CD4+CD25- T-cells from wild-type and gzmA-/- mice
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CD8+ and CD4+ cells
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additional information
GzmA/K transcript is detected in all tissues tested
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additional information
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GzmA/K transcript is detected in all tissues tested
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additional information
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enriched cytoplasmic granules
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additional information
granzyme A is produced by a variety of cell types involved in the immune response
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additional information
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granzyme A is produced by a variety of cell types involved in the immune response
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additional information
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enriched cytoplasmic granules
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additional information
granzyme A is produced by a variety of cell types involved in the immune response
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additional information
most of the GZMA-positive cells (over 95%) in non-infected mice are positive for the NK1.1 surface marker with a small proportion of CD8+ and CD4+ T cells, indicating that in the absence of infection GZMA expression in lungs is mainly restricted to natural killer (NK) cells. Conversely, four weeks post-infection, percentage of NK1.1-positive GZMA-expressing cells decreases to 80%, due to the substantial increase observed in the percentage of GZMA-positive CD8+ and CD4+ T cells, (15% and 5%, respectively). In concurrence with these observations, both frequency and absolute number of CD4+ and CD8+ GZMA-expressing cells dramatically increase in lungs upon infection. Tuberculosis infection also leads to an increase in the number of GZMA-expressing NK cells
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additional information
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most of the GZMA-positive cells (over 95%) in non-infected mice are positive for the NK1.1 surface marker with a small proportion of CD8+ and CD4+ T cells, indicating that in the absence of infection GZMA expression in lungs is mainly restricted to natural killer (NK) cells. Conversely, four weeks post-infection, percentage of NK1.1-positive GZMA-expressing cells decreases to 80%, due to the substantial increase observed in the percentage of GZMA-positive CD8+ and CD4+ T cells, (15% and 5%, respectively). In concurrence with these observations, both frequency and absolute number of CD4+ and CD8+ GZMA-expressing cells dramatically increase in lungs upon infection. Tuberculosis infection also leads to an increase in the number of GZMA-expressing NK cells
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additional information
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granzyme A is produced by a variety of cell types involved in the immune response
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additional information
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most of the GZMA-positive cells (over 95%) in non-infected mice are positive for the NK1.1 surface marker with a small proportion of CD8+ and CD4+ T cells, indicating that in the absence of infection GZMA expression in lungs is mainly restricted to natural killer (NK) cells. Conversely, four weeks post-infection, percentage of NK1.1-positive GZMA-expressing cells decreases to 80%, due to the substantial increase observed in the percentage of GZMA-positive CD8+ and CD4+ T cells, (15% and 5%, respectively). In concurrence with these observations, both frequency and absolute number of CD4+ and CD8+ GZMA-expressing cells dramatically increase in lungs upon infection. Tuberculosis infection also leads to an increase in the number of GZMA-expressing NK cells
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metabolism
CD8 T cells in psoriasis skinlesions display a dominant expression of granzyme A (GzmA) over granzyme B in the absence of perforin expression. Signals recruiting GzmA+ T cells into the skin and triggers of GzmA expression in the context of chronic inflammation, Tc17-polarizing conditions favour development of GzmA+GzmB-Prf-CD8 T-cells in the context of psoriasis
evolution
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the enzyme belongs to the granzyme serine protease family, key effector molecules expressed by cytotoxic lymphocytes. Peptide substrate specificity profile of mouse and human granzyme A, overview
evolution
the enzyme belongs to the granzyme serine protease family, key effector molecules expressed by cytotoxic lymphocytes. Peptide substrate specificity profile of mouse and human granzyme A, overview
malfunction
even though granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of Mycobacterium tuberculosis infection
malfunction
phenotypic characterization of gzmA-/- regulatory T cells (Tregs) efficiently homing to secondary lymphoid organs, GzmA-/- Tregs home efficiently to secondary lymphoid organs, overview. No difference between wild-type and GZMA-/- mice in Treg numbers in spleen and peripheral lymph nodes. Enzyme-deficient gzmA-/- Tregs cannot efficiently protect from GvHD-related inflammation and organ destruction in the intestinal tract with relevant crypt apoptosis detected in the small and large intestine
malfunction
pneumonia is induced in wild-type and GzmA-deficient (GzmA-/-) mice by intranasal inoculation of Streptococcus pneumoniae. In separate experiments, wild-type and GzmA-/- mice are treated with natural killer (NK) cell depleting antibodies. Upon infection, GzmA-/- mice show a better survival and lower bacterial counts in bronchoalveolar lavage fluid (BALF) and distant body sites compared to the wild-type mice. Although NK cells show strong GzmA expression, NK cell depletion does not influence bacterial loads in either wild-type or GzmA-/- mice. GzmA deficiency has little impact on lung pathology during late stage pneumococcal pneumonia
malfunction
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pneumonia is induced in wild-type and GzmA-deficient (GzmA-/-) mice by intranasal inoculation of Streptococcus pneumoniae. In separate experiments, wild-type and GzmA-/- mice are treated with natural killer (NK) cell depleting antibodies. Upon infection, GzmA-/- mice show a better survival and lower bacterial counts in bronchoalveolar lavage fluid (BALF) and distant body sites compared to the wild-type mice. Although NK cells show strong GzmA expression, NK cell depletion does not influence bacterial loads in either wild-type or GzmA-/- mice. GzmA deficiency has little impact on lung pathology during late stage pneumococcal pneumonia
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malfunction
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even though granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of Mycobacterium tuberculosis infection
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physiological function
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in filarial infection with Litomosoides sigmodontis, worm loads are significantly reduced in gzmA/gzmB and in gzmB knockout mice during the whole course of infection, but enhanced only early in gzmA knockout compared with wild-type mice. GzmA/gzmB deficiency is associated with a defense-promoting Th2 cytokine and Ab shift, enhanced early inflammatory gene expression, and a trend of reduced alternatively activated macrophage induction, whereas gzmA deficiency is linked with reduced inflammation and a trend toward increased alternatively activated macrophages
physiological function
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recombinant GrA promotes release of interleukin IL-8 from A-549 cells, without involvement of protease-activated receptor-1. Release is inhibited by taxol
physiological function
the human enzyme shows only slight cytotoxic potential in P815 mastocytoma target cells with streptolysin O
physiological function
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the murine enzyme shows a high cytotoxic potential in P815 mastocytoma target cells with streptolysin O
physiological function
wild-type and granzyme A-deficient mice eliminate the mouse pathogen Brucella microti from liver and spleen within 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. Only gzmA-/- mice exhibit increased survival, which correlated with reduced proinflammatory cytokines, due to depletion of natural killer cells. Infection-related pathology, but not bacterial clearance, appears to require the enzyme
physiological function
granzyme A contributes to the early inflammatory response in the lung. Granzyme A (GzmA) impairs host defense during Streptococcus pneumoniae pneumonia, role of GzmA on the host response during pneumococcal pneumonia, overview
physiological function
granzyme A contributes to the early inflammatory response in the lung. Granzyme A (GzmA) plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on natural killer cells. GzmA enhances bacterial dissemination and mortality in pneumococcal pneumonia
physiological function
granzyme A is expressed in mouse lungs during Mycobacterium tuberculosis strain H37Rv infection but does not contribute to protection in vivo. Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis
physiological function
granzyme A is required for regulatory T-cell mediated prevention of gastrointestinal graft-versus-host disease. Analysis of the role of granzyme A (GZMA) in a haploidentical murine graft-versus-host disease (GvHD) model using gzmA-/- donor regulatory T cells (Tregs) to clarify the functional relevance of GZMA for Treg-mediated suppression of GvHD. GZMA expressing Tregs protect against GvHD-related tissue damage of the intestine
physiological function
histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells. A fast-migrating histone H4 fragment is detected in cells undergoing staurosporine-induced cell death. Treatment with caspase inhibitors (inhibitors of caspase-6 (Z-VEID-FMK) and caspase-9 (Z-LEHD-FMK)) increases both cell death and histone H4 cleavage. The enzyme cleaves the N-terminal tail pf H4. The cleavage of the histone H4 tail by GzmA contributes to the disintegration of chromosomes during the cell death process. The SET complex is normally located in the endoplasmic reticulum, but it translocates to the nucleus in response to reactive oxygen species produced by GzmA-mediated cleavage of NADH dehydrogenase (ubiquinone) Fe-S protein 3. GzmA is mobilized in the nucleus where many of its known substrates reside. In the nucleus, GzmA digests three components of the SET complex: SET, high-mobility group protein B2, and apurinic/apyrimidinic endonuclease. SET is an inhibitor of the SET complex endonuclease NM23-H1. GzmA degrades the linker histone H1 and removes the tails from core histones H2 and H3, opening up the chromatin and making it accessible to nucleases
physiological function
interleukin-17 induced secretion of the cytokines interleukin-6, interleukin-8 and interleukin-23, whereas GzmA treatment alone does not induce secretion of inflammatory mediators. The combination of GzmA and interleukin-17 significantly increases the release of the proinflammatory chemokines CXCL 1, CXCL 12, and CCL 4 compared to interleukin-17 stimulation alone, but does not alter the levels of interleukin-17-induced cytokines interleukin-6, interleukin-8 and interleukin-23. GzmA neither promotes proliferation nor affects interleukin-17-induced keratinocyte differentiation status as measured by gene expression of MKI67, IVL, KRT16 or KRT10
physiological function
-
wild-type and granzyme A-deficient mice eliminate the mouse pathogen Brucella microti from liver and spleen within 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. Only gzmA-/- mice exhibit increased survival, which correlated with reduced proinflammatory cytokines, due to depletion of natural killer cells. Infection-related pathology, but not bacterial clearance, appears to require the enzyme
-
physiological function
-
granzyme A contributes to the early inflammatory response in the lung. Granzyme A (GzmA) plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on natural killer cells. GzmA enhances bacterial dissemination and mortality in pneumococcal pneumonia
-
physiological function
-
granzyme A is expressed in mouse lungs during Mycobacterium tuberculosis strain H37Rv infection but does not contribute to protection in vivo. Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis
-
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Mus musculus (P11032), Homo sapiens (P12544), Homo sapiens, Mus musculus C57BL/6 (P11032)
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Homo sapiens (P12544)
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Homo sapiens (P12544)
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Granzyme a is required for regulatory T-cell mediated prevention of gastrointestinal graft-versus-host disease
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Mus musculus (P11032), Mus musculus
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Mus musculus (P11032), Mus musculus, Mus musculus C57BL/6 (P11032)
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