Two CD95 (APO-1/Fas) signaling pathways

Scaffidi, Carsten; Fulda, Simone; Srinivasan, Anu; Friesen, Claudia; Li, Feng; Tomaselli, Kevin J.; Debatin, Klaus‐Michael; Krammer, Peter H.; Peter, Marcus E.

doi:10.1093/emboj/17.6.1675

Cited by 2,760 publications

(2,472 citation statements)

References 68 publications

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“…caspase-3). 20,21 The intrinsic pathway can be activated by agents that directly target the mitochondria without activation of caspase 8. In this study, the P2-Receptor ATP interaction resulted in the activation of the second pathway including cytochrome c release.…”

Section: Discussionmentioning

confidence: 99%

Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding

Selzner

Graf

et al. 2004

Cell Death Differ

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Although exposure of cells to extreme hypotonic stress appears to be a purely experimental set up, it has found an application in clinical routine. For years, surgeons have washed the abdominal cavity with distilled water to lyse isolated cancer cells left after surgery. No data are available supporting this practice or evaluating the potential mechanisms of cell injury under these circumstances. Recent evidence indicates that increases in cell volume stimulate release of adenosine triphosphate and autocrine stimulation of purinergic (P2) receptors in the plasma membrane of certain epithelial cell types. Under physiological conditions, purigenic stimulation can contribute to cell volume recovery through activation of solute efflux. In addition, adenosine triphosphate-P2 receptor binding might trigger other mechanisms affecting cell viability after profound hypotonic stress. This study demonstrates a novel pathway of cell death by apoptosis in human colon cancer cells following a short hypotonic stress. This pathway is induced by transitory cell swelling which leads to extracellular release of adenosine triphosphate (ATP) and specific binding of ATP to P2 receptors (probably P2X7). Extracellular ATP induced activation of caspases 3 and 8, annexin V, release of cytochrome c, and eventually cell death. The effect of ATP can be blocked by addition of (i) apyrase to hydrolyse extracellular ATP and (ii) suramin, a P2 receptor antagonist. Finally, (iii) gadolinium pretreatment, a blocker of ATP release, reduces sensitivity of the cells to hypotonic stress. The adenosine triphosphate-P2 receptor cell death pathway suggests that autocrine/paracrine signaling may contribute to regulation of viability in certain cancer cells disclosed with this pathway.

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Section: Discussionmentioning

confidence: 99%

Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding

Selzner

Graf

et al. 2004

Cell Death Differ

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“…The death receptors family includes the tumor necrosis factor-α (TNF-α) receptor -1 and CD95/Fas (the receptor of CD95L/FasL) [21,22]. The netrin-1 receptors DCC and UNC5H-1, -2 and -3, on the other hand, represent prototypic dependency receptors [23].…”

Section: Intrinsic and Extrinsic Apoptosis Pathwaysmentioning

confidence: 99%

“…Indeed, caspase-8 induces the proteolytic maturation of the BH3-only protein Bid, which, in its truncated form (tBid) translocates to mitochondria and favors MMP [21,26,27]. tBid acts at mitochondria through the cardiolipin-facilitated interaction with other pro-apoptotic members of the Bcl-2 family (e.g.…”

Section: Intrinsic and Extrinsic Apoptosis Pathwaysmentioning

confidence: 99%

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

et al. 2007

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Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable degree. OM permeabilization culminates in the release of proteins that normally are confined in the mitochondrial intermembrane space (IMS), including caspase activators (e.g. cytochrome c) and caspase-independent death effectors (e.g. apoptosis-inducing factor). Partial IM permeabilization disrupts mitochondrial ion and volume homeostasis and dissipates the mitochondrial transmembrane potential ( m ). The assessment of early mitochondrial alterations allows for the identification of cells that are committed to die but have not displayed yet the apoptotic phenotype. Several

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“…Two signaling pathways (type I and II) have been identified. [16][17][18][19] TNFR-1 and TNFR-2 have significant homology in their extracellular domains; however, their cytoplasmic domains are different.…”

Section: Introductionmentioning

confidence: 99%

The influence of α1-antagonist on the expression pattern of TNF receptor family in primary culture of prostate epithelial cells from BPH patients

Drewa

Wolski

Misterek

et al. 2007

Prostate Cancer Prostatic Dis

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Doxazosin triggers apoptosis via an imprecisely defined receptor mechanism that is related to tumor necrosis factor receptors (TNFRs). The aim of this study was to determine CD95, TNFR-1, TNFR-2, CD40 expression in primary prostate epithelial cultures incubated with doxazosin. Epithelial cultures were cultivated from 10 benign prostate hyperplasia patients. The cells were incubated with 20, 50 and 80 lM of doxazosin. Apoptosis was confirmed by fluorescence microscopy and flow cytometry. The cells were analyzed for expression of FAS, CD40, TNFR-1 and TNFR-2 by flow cytometry. Early apoptotic cells were present in all groups. A positive correlation was noticed between doxazosin dose and TNFR-1-, -2-positive cells. A decrease of CD40-positive cell population was observed in the lowest concentration. A decrease of mean fluorescence intensity signal of CD40 and CD95 was observed in the lowest concentration. Doxazosin-triggered apoptosis was doseindependent. The initiation of apoptosis was a result of receptors 'crosstalk' rather than a single receptor pathway activation. TNF receptor self-assembly process should be checked as a potential mechanism leading to apoptosis after doxazosin treatment.

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Two CD95 (APO-1/Fas) signaling pathways

Cited by 2,760 publications

References 68 publications

Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding

Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

The influence of α1-antagonist on the expression pattern of TNF receptor family in primary culture of prostate epithelial cells from BPH patients

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