The Experts below are selected from a list of 16533 Experts worldwide ranked by ideXlab platform
Carol L Pickett - One of the best experts on this subject based on the ideXlab platform.
-
interactions of campylobacter jejuni cytolethal distending toxin subunits cdta and cdtc with hela cells
Infection and Immunity, 2003Co-Authors: Robert B Lee, D L Cottle, Duane C Hassane, Carol L PickettAbstract:Campylobacter jejuni produces a toxin, called cytolethal distending toxin (CDT), which causes Direct DNA Damage leading to invocation of DNA Damage checkpoint pathways. The affected cells arrest in G1 or G2 and eventually die. CDT consists of three protein subunits, CdtA, CdtB, and CdtC, with CdtB recently identified as a nuclease. However, little is known about the functions of CdtA or CdtC. In this work, enzyme-linked immunosorbent assay-based experiments were used to show, for the first time, that both CdtA and CdtC bound with specificity to the surface of HeLa cells, whereas CdtB did not. Varying the order of the addition of subunits for reconstitution of the holotoxin had no effect on activity. In addition, mutants containing deletions of conserved regions of CdtA and CdtC were able to bind to the surface of HeLa cells but were not able to participate in holotoxin assembly. Finally, both Cdt mutant subunits were able to effectively compete with CDT holotoxin in the HeLa cell binding assay.
-
campylobacter jejuni cytolethal distending toxin promotes DNA repair responses in normal human cells
Infection and Immunity, 2003Co-Authors: Duane C Hassane, Robert B Lee, Carol L PickettAbstract:Cytolethal distending toxin (CDT) is a multisubunit protein found in various gram-negative bacterial pathogens of humans which is thought to cause cell death by Direct DNA Damage of host cells. We sought to determine if a cellular response to DNA Damage could be detected by exogenous addition of the holotoxin. Exogenous addition of the Campylobacter jejuni 81-176 CDT to primary human fibroblasts resulted in formation of Rad50 foci, which are formed around double-stranded-DNA breaks. Moreover, such foci are formed in both proliferating and nonproliferating cells that are treated with C. jejuni CDT. Fibroblasts that were intoxicated and later stimulated to proliferate failed to divide and remained arrested in the G1 phase of the cell cycle.
Duane C Hassane - One of the best experts on this subject based on the ideXlab platform.
-
interactions of campylobacter jejuni cytolethal distending toxin subunits cdta and cdtc with hela cells
Infection and Immunity, 2003Co-Authors: Robert B Lee, D L Cottle, Duane C Hassane, Carol L PickettAbstract:Campylobacter jejuni produces a toxin, called cytolethal distending toxin (CDT), which causes Direct DNA Damage leading to invocation of DNA Damage checkpoint pathways. The affected cells arrest in G1 or G2 and eventually die. CDT consists of three protein subunits, CdtA, CdtB, and CdtC, with CdtB recently identified as a nuclease. However, little is known about the functions of CdtA or CdtC. In this work, enzyme-linked immunosorbent assay-based experiments were used to show, for the first time, that both CdtA and CdtC bound with specificity to the surface of HeLa cells, whereas CdtB did not. Varying the order of the addition of subunits for reconstitution of the holotoxin had no effect on activity. In addition, mutants containing deletions of conserved regions of CdtA and CdtC were able to bind to the surface of HeLa cells but were not able to participate in holotoxin assembly. Finally, both Cdt mutant subunits were able to effectively compete with CDT holotoxin in the HeLa cell binding assay.
-
campylobacter jejuni cytolethal distending toxin promotes DNA repair responses in normal human cells
Infection and Immunity, 2003Co-Authors: Duane C Hassane, Robert B Lee, Carol L PickettAbstract:Cytolethal distending toxin (CDT) is a multisubunit protein found in various gram-negative bacterial pathogens of humans which is thought to cause cell death by Direct DNA Damage of host cells. We sought to determine if a cellular response to DNA Damage could be detected by exogenous addition of the holotoxin. Exogenous addition of the Campylobacter jejuni 81-176 CDT to primary human fibroblasts resulted in formation of Rad50 foci, which are formed around double-stranded-DNA breaks. Moreover, such foci are formed in both proliferating and nonproliferating cells that are treated with C. jejuni CDT. Fibroblasts that were intoxicated and later stimulated to proliferate failed to divide and remained arrested in the G1 phase of the cell cycle.
Robert B Lee - One of the best experts on this subject based on the ideXlab platform.
-
interactions of campylobacter jejuni cytolethal distending toxin subunits cdta and cdtc with hela cells
Infection and Immunity, 2003Co-Authors: Robert B Lee, D L Cottle, Duane C Hassane, Carol L PickettAbstract:Campylobacter jejuni produces a toxin, called cytolethal distending toxin (CDT), which causes Direct DNA Damage leading to invocation of DNA Damage checkpoint pathways. The affected cells arrest in G1 or G2 and eventually die. CDT consists of three protein subunits, CdtA, CdtB, and CdtC, with CdtB recently identified as a nuclease. However, little is known about the functions of CdtA or CdtC. In this work, enzyme-linked immunosorbent assay-based experiments were used to show, for the first time, that both CdtA and CdtC bound with specificity to the surface of HeLa cells, whereas CdtB did not. Varying the order of the addition of subunits for reconstitution of the holotoxin had no effect on activity. In addition, mutants containing deletions of conserved regions of CdtA and CdtC were able to bind to the surface of HeLa cells but were not able to participate in holotoxin assembly. Finally, both Cdt mutant subunits were able to effectively compete with CDT holotoxin in the HeLa cell binding assay.
-
campylobacter jejuni cytolethal distending toxin promotes DNA repair responses in normal human cells
Infection and Immunity, 2003Co-Authors: Duane C Hassane, Robert B Lee, Carol L PickettAbstract:Cytolethal distending toxin (CDT) is a multisubunit protein found in various gram-negative bacterial pathogens of humans which is thought to cause cell death by Direct DNA Damage of host cells. We sought to determine if a cellular response to DNA Damage could be detected by exogenous addition of the holotoxin. Exogenous addition of the Campylobacter jejuni 81-176 CDT to primary human fibroblasts resulted in formation of Rad50 foci, which are formed around double-stranded-DNA breaks. Moreover, such foci are formed in both proliferating and nonproliferating cells that are treated with C. jejuni CDT. Fibroblasts that were intoxicated and later stimulated to proliferate failed to divide and remained arrested in the G1 phase of the cell cycle.
Jihhwa Guh - One of the best experts on this subject based on the ideXlab platform.
-
terfenadine induces anti proliferative and apoptotic activities in human hormone refractory prostate cancer through histamine receptor independent mcl 1 cleavage and bak up regulation
Naunyn-schmiedebergs Archives of Pharmacology, 2014Co-Authors: Weiting Wang, Yenhui Chen, Juiling Hsu, Wohnjenn Leu, Shehung Chan, Lihching Hsu, Jihhwa GuhAbstract:Although the results of several studies have underscored the regulatory effect of H1-histamine receptors in cell proliferation of some cancer cell types, its effect in prostate cancers remains unclear. We have therefore studied the effect of terfenadine (an H1-histamine receptor antagonist) in prostate cancer cell lines. Our data demonstrate that terfenadine was effective against PC-3 and DU-145 cells (two prostate cancer cell lines). In contrast, based on the sulforhodamine B assay, loratadine had less potency while fexofenadine and diphenhydramine had little effect. Terfenadine induced the cleavage of Mcl-1 cleavage into a pro-apoptotic 28-kDa fragment and up-regulation of Bak, resulting in the loss of mitochondrial membrane potential (ΔΨm) and the release of cytochrome c and apoptosis-inducing factor into the cytosol. The activation of caspase cascades was detected to be linked to terfenadine action. Bak up-regulation was also examined at both the transcriptional and translational levels, and Bak activation was validated based on conformational change to expose the N terminus. Terfenadine also induced an inDirect-but not Direct-DNA Damage response through the cleavage and activation of caspase-2, phosphorylation and activation of Chk1 and Chk2 kinases, phosphorylation of RPA32 and acetylation of Histone H3; these processes were highly correlated to severe mitochondrial dysfunction and the activation of caspase cascades. In conclusion, terfenadine induced apoptotic signaling cascades against HRPCs in a sequential manner. The exposure of cells to terfenadine caused the up-regulation and activation of Bak and the cleavage of Mcl-1, leading to the loss of ΔΨm and activation of caspase cascades which further resulted in DNA Damage response and cell apoptosis.
Werner Geurtsen - One of the best experts on this subject based on the ideXlab platform.
-
genotoxic and mutagenic potential of camphorquinone in l5178 tk mouse lymphoma cells
Dental Materials, 2018Co-Authors: Joachim Volk, Christina Ziemann, Gabriele Leyhausen, Werner GeurtsenAbstract:Abstract Objectives Camphorquinone (CQ) is the most important photoinitiator used in dental composite resins. Sparse data indicate a mutagenic potential of CQ. Therefore, it was aim of this study to evaluate the cytotoxicity, genotoxicity, and mutagenicity of CQ in L5178Y TK+/− mouse lymphoma cells. Methods L5178Y/TK+/− cells were exposed to different concentrations of non-irradiated CQ (0.25–2.5 mM). Cytotoxicity was evaluated by propidium iodide assay, determination of suspension growth rate, relative total growth and the mitotic index. Intracellular levels of reactive oxygen/nitrogen species (ROS/RNS) were quantified by 2′,7′-dichlorofluoresceine diacetate (DCFH-DA). Early induction of DNA strand breaks and oxidative DNA base lesions was assessed using the 8-hydroxyguanine DNA-glycosylase 1 (hOGG1)-modified alkaline comet assay, whereas mutagenicity of CQ was determined in the mouse lymphoma TK assay (MLA), according to OECD Guideline No. 490. Results CQ (0.5–2.5 mM) induced concentration- and time-dependent inhibition of cell growth associated with increased ROS/RNS production, amounting to 2342% ± 1108% of controls after 90 min at 2.5 mM. Additionally, CQ concentration-dependently caused Direct DNA-Damage, i.e. formation of DNA strand breaks and 8-hydroxy-2′-deoxyguanosine. Whereas the MLA indicated lack of mutagenicity of CQ after a 4 h of treatment, CQ concentration-dependently increased total mutant frequency (MF) after 24 h (about 2-fold at 2.5 mM). But, based on the global evaluation factor concept, increase in MF did not reach biologically relevance. Significance CQ induced concentration-dependent, cytotoxic and genotoxic effects in L5178Y/TK+/− cells, most likely due to oxidative stress, but without mediating obvious biological relevant mutagenicity.