The Experts below are selected from a list of 27834 Experts worldwide ranked by ideXlab platform
Scott H Kaufmann - One of the best experts on this subject based on the ideXlab platform.
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phorbol 12 myristate 13 acetate inhibits death receptor mediated apoptosis in Jurkat Cells by disrupting recruitment of fas associated polypeptide with death domain
Journal of Biological Chemistry, 2002Co-Authors: Xue Wei Meng, Michael P Heldebrant, Scott H KaufmannAbstract:Abstract Regulation of death receptor-mediated apoptosis is incompletely understood. Previous studies have demonstrated that phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, inhibits Fas (CD95)-mediated apoptosis in Jurkat (type II) Cells but not SKW6.4 (type I) Cells. In this study, we demonstrated that PMA also protects Jurkat Cells from apoptosis induced by tumor necrosis factor-α and the tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL). Interestingly, PMA failed to protect Jurkat Cells from apoptosis induced by other agents, including etoposide, camptothecin, and γ-irradiation. Analysis of the initial events induced by agonistic anti-Fas antibodies revealed that PMA inhibited Fas binding to Fas-associated polypeptide with death domain (FADD) in Jurkat Cells but not in SKW6.4 Cells. Although the protein kinase inhibitor bisindoylmaleimide VIII increased apoptosis induced by agonistic anti-Fas antibody, tumor necrosis factor-α, and TRAIL, these effects were not observed with the protein kinase C inhibitor H7 and were not associated with increased FADD recruitment to Fas. These results indicate that PMA inhibits death signaling induced by a number of discrete receptors and suggest that the effects are mediated at the level of receptor-mediated adaptor molecule recruitment.
Chengdeng Kuo - One of the best experts on this subject based on the ideXlab platform.
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norcantharidin preferentially induces apoptosis in human leukemic Jurkat Cells without affecting viability of normal blood mononuclear Cells
Food and Chemical Toxicology, 2007Co-Authors: Huifen Liao, Yujen Chen, Chinhung Chou, Chengdeng KuoAbstract:Abstract Norcantharidin (NCTD) is known to have anti-cancer potentials. The aim of this study was to assess the apoptosis-inducing effect of NCTD on human leukemic Jurkat Cells. We found that NCTD preferentially inhibited the growth of Jurkat Cells in a dose- and time-dependent manner, but not the growth of normal blood mononuclear Cells (MNC). Pretreatment with agonistic (CH-11) and antagonistic (ZB4) Fas antibodies on Jurkat Cells showed that NCTD-induced apoptosis might not involve Fas–FasL signaling. Flow cytometric assay of Jurkat Cells treated with NCTD showed a markedly increased sub-G1 DNA phase and cell cycle arrest at S phase. Western blot analysis of NCTD-treated Cells showed increased expressions of cytochrome c, active caspase-9 and -3, and cleavage of poly(ADP–ribose) polymerase (PARP), but the expressions of Bcl-2, Bax and apoptosis-inducing factor were not increased. The transcription factor STAT1 was translocated from cytosol to nucleus. Pancaspase inhibitor z-VAD-FMK not only limited the level of sub-G1 phase, but also prevented the degradation of PARP in NCTD-treated Cells. The NCTD-induced cell cycle arrest and apoptosis were mediated through the regulation of ataxia-telangiectasia mutated (ATM), rather than P63 protein. The conditioned medium produced from human MNC (NCTD–MNC-CM) increased the percentage of apoptotic Cells and the expression of PARP cleavage in Jurkat Cells. Protein array assay of NCTD–MNC-CM showed 32.4- and 6.2-folds increases in TNF-α and GM–CSF, respectively, and the expression of MCP-1, GRO, RANTES and IL-10 was decreased. We conclude that NCTD can induce apoptosis in human leukemic Jurkat Cells via a caspase-dependent pathway without affecting the viability of normal MNC, and that the apoptosis-inducing effect of NCTD can also be achieved by soluble cytokines produced from peripheral MNC.
Kojiro Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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prolonged high glucose suppresses phorbol 12 myristate 13 acetate and ionomycin induced interleukin 2 mrna expression in Jurkat Cells
Biochimica et Biophysica Acta, 2009Co-Authors: Koji Higai, Masatoshi Tsukada, Yumiko Moriya, Yutaro Azuma, Kojiro MatsumotoAbstract:Abstract Background The disturbance of immunological responses is a complication of diabetes mellitus. Methods and Results We cultured Jurkat Cells in 11.1 (normal) and 22.2 mmol/l (high) glucose for 12 weeks and stimulated them with 10 nmol/l phorbol 12-myristate 13-acetate (PMA) and 500 nmol/l ionomycin. RT-PCR revealed that induced interleukin (IL)-2 mRNA expression levels were suppressed in high glucose cultures compared to those in normal glucose. Promoter activities of IL-2, nuclear factor of activated T Cells (NFAT), and activator protein-1 (AP-1), after 6 h stimulation with PMA and ionomycin, gradually decreased in high glucose cultures to approximately 20% of those in normal glucose at 12 weeks. The prolonged culture in high glucose increased inducible cAMP early repressor (ICER) II mRNA and protein levels, and overexpression of ICER II dose-dependently suppressed promoter activities of IL-2, NFAT, and AP-1. Moreover, ICER II mRNA expression was transiently induced by stimulation with PMA and ionomycin in normal glucose cultures; however, with high glucose, the induction disappeared. Conclusion These results indicate that ICER II protein accumulates during prolonged culture in high glucose and suppresses IL-2 mRNA expression in Jurkat Cells.
Yewmin Tzeng - One of the best experts on this subject based on the ideXlab platform.
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cytotoxic constituents from andrographis paniculata induce cell cycle arrest in Jurkat Cells
Phytotherapy Research, 2008Co-Authors: Madamanchi Geethangili, Yerra Koteswara Rao, Shihhua Fang, Yewmin TzengAbstract:Herbal medicines are now attracting attention as potential sources of anticancer agents. Andrographis paniculata is a traditionally used anticancer herb in Indian and Chinese herbal medicine. Phytochemical investigation of the ethanol extract of the aerial parts of this herb resulted in the isolation of 14 compounds including flavonoids and labdane diterpenoids. This is the first isolation of compound 6 from a natural source, and the aerial parts of A. paniculata are a rich source for the molecule andrographolide (9, 1.375%, w/w). The structures of the isolated compounds were established by means of spectral data. The cytotoxic activities of these isolates were evaluated against Jurkat, PC-3, HepG2 and Colon 205 tumor Cells, and normal Cells PBMCs. The bioactivity assays showed that metabolites 1–4 and 6–8 exhibited moderate cytotoxic activity against Jurkat, PC-3 and Colon 205 cell lines, where compound 6 had IC50 values of 0.05, 0.07 and 0.05 mm, respectively. Further, among these effective compounds, 3 and 6 selectively blocked the cell cycle progression at G0/G1, while 1, 2, 4, 7 and 8 blocked the same at G2/M phase of the Jurkat cell line. This is the first cell cycle analysis for the above mentioned isolates on the Jurkat Cells. Therefore, these plant-derived compounds may play a role in the prevention and/or management of cancer. Copyright © 2008 John Wiley & Sons, Ltd.
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cytotoxic constituents from andrographis paniculata induce cell cycle arrest in Jurkat Cells
Phytotherapy Research, 2008Co-Authors: Madamanchi Geethangili, Yerra Koteswara Rao, Shihhua Fang, Yewmin TzengAbstract:Herbal medicines are now attracting attention as potential sources of anticancer agents. Andrographis paniculata is a traditionally used anticancer herb in Indian and Chinese herbal medicine. Phytochemical investigation of the ethanol extract of the aerial parts of this herb resulted in the isolation of 14 compounds including flavonoids and labdane diterpenoids. This is the first isolation of compound 6 from a natural source, and the aerial parts of A. paniculata are a rich source for the molecule andrographolide (9, 1.375%, w/w). The structures of the isolated compounds were established by means of spectral data. The cytotoxic activities of these isolates were evaluated against Jurkat, PC-3, HepG2 and Colon 205 tumor Cells, and normal Cells PBMCs. The bioactivity assays showed that metabolites 1-4 and 6-8 exhibited moderate cytotoxic activity against Jurkat, PC-3 and Colon 205 cell lines, where compound 6 had IC(50) values of 0.05, 0.07 and 0.05 mm, respectively. Further, among these effective compounds, 3 and 6 selectively blocked the cell cycle progression at G0/G1, while 1, 2, 4, 7 and 8 blocked the same at G2/M phase of the Jurkat cell line. This is the first cell cycle analysis for the above mentioned isolates on the Jurkat Cells. Therefore, these plant-derived compounds may play a role in the prevention and/or management of cancer.
John D Robertson - One of the best experts on this subject based on the ideXlab platform.
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caspase 9 activation by the apoptosome is not required for fas mediated apoptosis in type ii Jurkat Cells
Journal of Biological Chemistry, 2009Co-Authors: Mary E Shawgo, Shary N Shelton, John D RobertsonAbstract:Activation of executioner caspases during receptor-mediated apoptosis in type II Cells requires the engagement of the mitochondrial apoptotic pathway. Although it is well established that recruitment of mitochondria in this context involves the cleavage of Bid to truncated Bid (tBid), the precise post-mitochondrial signaling responsible for executioner caspase activation is controversial. Here, we used distinct clones of type II Jurkat T-lymphocytes in which the mitochondrial apoptotic pathway had been inhibited to investigate the molecular requirements necessary for Fas-induced apoptosis. Cells overexpressing either Bcl-2 or Bcl-xL were protected from apoptosis induced by agonistic anti-Fas antibody. By comparison, Apaf-1-deficient Jurkat Cells were sensitive to anti-Fas, exhibiting Bid cleavage, Bak activation, the release of cytochrome c and Smac, and activation of executioner caspase-3. Inhibiting downstream caspase activation with the pharmacological inhibitor Z-DEVD-fmk or by expressing the BIR1/BIR2 domains of X-linked inhibitor of apoptosis protein (XIAP) decreased all anti-Fas-induced apoptotic changes. Additionally, pretreatment of Bcl-xL-overexpressing Cells with a Smac mimetic sensitized these Cells to Fas-induced apoptosis. Combined, our findings strongly suggest that Fas-mediated activation of executioner caspases and induction of apoptosis do not depend on apoptosome-mediated caspase-9 activation in prototypical type II Cells.
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cleavage of bid by executioner caspases mediates feed forward amplification of mitochondrial outer membrane permeabilization during genotoxic stress induced apoptosis in Jurkat Cells
Journal of Biological Chemistry, 2009Co-Authors: Shary N Shelton, Mary E Shawgo, John D RobertsonAbstract:The extent to which the BH3-only protein Bid is important for intrinsic (mitochondria-mediated) apoptotic cell death induced by genotoxic stress remains controversial. In the present study, we examine this issue using a panel of gene-manipulated Bax-deficient Jurkat T-lymphocytes. Cells stably depleted of Bid were far less sensitive than control-transfected Cells to etoposide-induced apoptosis. In particular, drug-induced Bak activation, cytochrome c release, loss of mitochondrial membrane potential, and caspase activation were all decreased in Cells lacking Bid. Reconstitution experiments using recombinant proteins and permeabilized Bid-deficient Cells demonstrated that truncated Bid (tBid), but not full-length Bid, potently induced Bak activation and the release of cytochrome c. Further, caspase-8-deficient Jurkat Cells efficiently cleaved Bid and were sensitive to drug-induced apoptosis. By comparison, Apaf-1-deficient Cells, as well as Cells overexpressing full-length X-linked inhibitor of apoptosis protein (XIAP) or the BIR1/BIR2 domains of XIAP, failed to cleave Bid in response to genotoxic stress. These data suggest that tBid plays an important regulatory role in the execution of DNA damage-induced cytochrome c release and apoptosis. However, the fact that cleavage of Bid to tBid is mediated by executioner caspases suggests that a self-amplifying feed forward loop involving caspases, Bid, and mitochondria may help determine irreversible commitment to apoptosis.
