scholarly journals The 2-chlorodeoxyadenosine-induced cell death signalling pathway in human thymocytes is different from that induced by 2-chloroadenosine

1995 ◽  
Vol 311 (2) ◽  
pp. 585-588 ◽  
Author(s):  
Z Szondy
Keyword(s):  
Cell Death ◽  
Nucleoside Transport ◽  
Signalling Pathways ◽  
Deoxycytidine Kinase ◽  
Induce Cell Death ◽  
Kinase C ◽  
Transport Inhibitor ◽  
Dependent Cell ◽  
Nucleoside Transport Inhibitor ◽  
Induced Apoptosis

2-chloroadenosine induced DNA fragmentation and cell death in human thymocytes primarily by Ca(2+)-dependent mechanisms. Incubation of human thymocytes with 2-chlorodeoxyadenosine (5-1000 nM) also induced cell death (apoptosis) which was dependent on macromolecule synthesis and involved activation of an endonuclease which was inhibited by Zn2+. The effect of 2-chlorodeoxyadenosine was prevented by addition of dipyridamole, a strong nucleoside transport inhibitor, or of deoxycytidine, previously shown to compete for uptake by deoxycytidine kinase. 2-Chlorodeoxyadenosine-induced apoptosis did not involve increases in the cytosolic Ca2+ concentration, but required the presence of intracellular Ca2+. It was not inhibited by activators of protein kinase C previously shown to inhibit Ca(2+)-dependent cell death. Addition of 2-chlorodeoxyadenosine induced an increase in the amount of p53 in human thymocytes, while 2-chloroadenosine had no effect. These data suggest that 2-chloroadenosine and 2-chlorodeoxyadenosine induce cell death in human thymocytes via different signalling pathways.

Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1461-1468 ◽  
Author(s):  
Paul G. Ekert ◽  
Anissa M. Jabbour ◽  
Anand Manoharan ◽  
Jacki E. Heraud ◽  
Jai Yu ◽  
...  
Keyword(s):  
Cell Death ◽  
Family Members ◽  
Pi3 Kinase ◽  
Minor Role ◽  
Growth And Survival ◽  
Interleukin 3 ◽  
Dependent Cell ◽  
Induced Apoptosis ◽  
A Minor ◽  
Survival Signals

Growth and survival of hematopoietic cells is regulated by growth factors and cytokines, such as interleukin 3 (IL-3). When cytokine is removed, cells dependent on IL-3 kill themselves by a mechanism that is inhibited by overexpression of Bcl-2 and is likely to be mediated by proapoptotic Bcl-2 family members. Bad and Bim are 2 such BH3-only Bcl-2 family members that have been implicated as key initiators in apoptosis following growth factor withdrawal, particularly in IL-3-dependent cells. To test the role of Bad, Bim, and other proapoptotic Bcl-2 family members in IL-3 withdrawal-induced apoptosis, we generated IL-3-dependent cell lines from mice lacking the genes for Bad, Bim, Puma, both Bad and Bim, and both Bax and Bak. Surprisingly, Bad was not required for cell death following IL-3 withdrawal, suggesting changes to phosphorylation of Bad play only a minor role in apoptosis in this system. Deletion of Bim also had no effect, but cells lacking Puma survived and formed colonies when IL-3 was restored. Inhibition of the PI3 kinase pathway promoted apoptosis in the presence or absence of IL-3 and did not require Bad, Bim, or Puma, suggesting IL-3 receptor survival signals and PI3 kinase survival signals are independent.

scholarly journals TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
James A Rickard ◽  
Holly Anderton ◽  
Nima Etemadi ◽  
Ueli Nachbur ◽  
Maurice Darding ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcriptional Activity ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Inflammatory Phenotype ◽  
Dependent Cell ◽  
Perinatal Lethality ◽  
Induced Apoptosis ◽  
Deficient Mice

SHARPIN regulates immune signaling and contributes to full transcriptional activity and prevention of cell death in response to TNF in vitro. The inactivating mouse Sharpin cpdm mutation causes TNF-dependent multi-organ inflammation, characterized by dermatitis, liver inflammation, splenomegaly, and loss of Peyer's patches. TNF-dependent cell death has been proposed to cause the inflammatory phenotype and consistent with this we show Tnfr1, but not Tnfr2, deficiency suppresses the phenotype (and it does so more efficiently than Il1r1 loss). TNFR1-induced apoptosis can proceed through caspase-8 and BID, but reduction in or loss of these players generally did not suppress inflammation, although Casp8 heterozygosity significantly delayed dermatitis. Ripk3 or Mlkl deficiency partially ameliorated the multi-organ phenotype, and combined Ripk3 deletion and Casp8 heterozygosity almost completely suppressed it, even restoring Peyer's patches. Unexpectedly, Sharpin, Ripk3 and Casp8 triple deficiency caused perinatal lethality. These results provide unexpected insights into the developmental importance of SHARPIN.

Prevention of Catecholamine-Induced Cardiac Damage and Death with a Nucleoside Transport Inhibitor

1992 ◽  
Vol 20 (2) ◽  
pp. 173-178 ◽  
Author(s):  
Herman Van Belle ◽  
Willy Verheyen ◽  
Kris Ver Donck ◽  
Paul A. J. Janssen ◽  
J. Ian S. Robertson
Keyword(s):  
Nucleoside Transport ◽  
Cardiac Damage ◽  
Transport Inhibitor ◽  
Nucleoside Transport Inhibitor

scholarly journals 5-Aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved

2003 ◽  
Vol 370 (3) ◽  
pp. 1027-1032 ◽  
Author(s):  
José M. LÓPEZ ◽  
Antonio F. SANTIDRIÁN ◽  
Clara CAMPÀS ◽  
Joan GIL
Keyword(s):  
Protein Kinase ◽  
Cell Types ◽  
Jurkat Cells ◽  
Nucleoside Transport ◽  
Cytochrome C Release ◽  
Nucleotide Biosynthesis ◽  
Apoptotic Effect ◽  
Nucleoside Transport Inhibitor ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

5-Aminoimidazole-4-carboxamide (AICA) riboside, a precursor of purine nucleotide biosynthesis, induces apoptosis in Jurkat cells. Incorporation of AICAriboside into the cells is necessary for this effect since addition of nitrobenzylthioinosine, a nucleoside-transport inhibitor, completely protects Jurkat cells from apoptosis. Adenosine, but not other nucleosides, also protects Jurkat cells from AICAriboside-induced apoptosis. The apoptotic effect is caspase-dependent since caspases 9 and 3 are activated and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk) blocks apoptosis. Furthermore, AICAriboside induces mitochondrial cytochrome c release. AICAriboside, when phosphorylated to AICAribotide (ZMP), is a specific activator of the AMP-activated protein kinase (AMPK) in certain cell types. However, AICAriboside does not activate AMPK in Jurkat cells. Moreover, 5-iodotubercidin, an inhibitor of AICAriboside phosphorylation, does not inhibit apoptosis in Jurkat cells. These results indicate that AICAriboside induces apoptosis independently of ZMP synthesis and AMPK activation in Jurkat cells.

scholarly journals Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 630-637 ◽  
Author(s):  
Bing Z. Carter ◽  
Duncan H. Mak ◽  
Wendy D. Schober ◽  
Teresa McQueen ◽  
David Harris ◽  
...  
Keyword(s):  
Cell Death ◽  
Anticancer Agents ◽  
Chinese Herb ◽  
Mitochondrial Pathway ◽  
Leukemic Cells ◽  
Cytochrome C Release ◽  
Knock Out ◽  
Dependent Cell ◽  
Induced Apoptosis

Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook.f, has shown antitumor activities in a broad range of solid tumors. Here, we examined its effects on leukemic cells and found that, at 100 nM or less, it potently induced apoptosis in various leukemic cell lines and primary acute myeloid leukemia (AML) blasts. We then attempted to identify its mechanisms of action. Triptolide induced caspase-dependent cell death accompanied by a significant decrease in XIAP levels. Forced XIAP overexpression attenuated triptolide-induced cell death. Triptolide also decreased Mcl-1 but not Bcl-2 and Bcl-XL levels. Bcl-2 overexpression suppressed triptolide-induced apoptosis. Further, triptolide induced loss of the mitochondrial membrane potential and cytochrome C release. Caspase-9 knock-out cells were resistant, while caspase-8–deficient cells were sensitive to triptolide, suggesting criticality of the mitochondrial but not the death receptor pathway for triptolide-induced apoptosis. Triptolide also enhanced cell death induced by other anticancer agents. Collectively, our results demonstrate that triptolide decreases XIAP and potently induces caspase-dependent apoptosis in leukemic cells mediated through the mitochondrial pathway at low nanomolar concentrations. The potent antileukemic activity of triptolide in vitro warrants further investigation of this compound for the treatment of leukemias and other malignancies.

Sign in / Sign up

Export Citation Format

Share Document