Environmental Chemical-Induced Bone Marrow B Cell Apoptosis: Death Receptor-Independent Activation of a Caspase-3 to Caspase-8 Pathway

Ryu, Heui-Young; Emberley, Jessica K.; Schlezinger, Jennifer J.; Allan, Lenka L.; Na, Songqing; Sherr, David H.

doi:10.1124/mol.105.014712

Cited by 26 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with previous work showing that caspase-8 activation can occur in a manner independent of FADD (Stupack et al, 2001). As keratinocytes undergo anoikis after the early activation of caspase-8, without the involvement of FADD, one might postulate that caspase-8 is activated downstream of caspase-3, in agreement with previous reports of death receptor-independent apoptosis (Ryu et al, 2005). Alternatively, caspase-8 activation could occur downstream of caspase-9 as an amplification loop of the intrinsic apoptotic pathway (Grossmann et al, 2001).…”

Section: Discussionsupporting

confidence: 89%

A Previously Unreported Function of β1B Integrin Isoform in Caspase-8-Dependent Integrin-Mediated Keratinocyte Death

Lotti

Marconi

Truzzi

et al. 2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Integrins regulate adhesive cell-matrix interactions and mediate survival signals. On the other hand, unligated or free cytoplasmic fragments of integrins induce apoptosis in many cell types (integrin-mediated death). We have previously shown that β(1) integrin expression protects keratinocyte stem cells from anoikis, whereas the role of the β(1)B integrin isoform has not been clarified. In this study we report that suspended keratinocytes undergo apoptosis through the activation of caspase-8, independently of the Fas/Fas ligand system. Indeed, anti-β(1) integrin-neutralizing antibodies induced apoptosis in short hairpin RNA Fas-associated death domain-treated cells. Moreover, before and during suspension, caspase-8 directly associated with β(1) integrin, which in turn internalized and progressively degraded, shedding the cytoplasmic domain. β(1)B was expressed only in the cytoplasm in a perinuclear manner and remained unaltered during suspension. At 24 hours, as β(1)A was located close to the nucleus, β(1)B colocalized with β(1)A and coimmunoprecipitated with caspase-8. Caspase-8 was activated earlier in β(1)B integrin-transfected keratinocytes, and these cells underwent a higher rate of apoptosis than mock cells. In contrast, caspase-8 was not activated in small interfering RNA (siRNA) β(1)B-transfected cells. These results indicate that when β(1)A is unligated, β(1)B is responsible for "integrin-mediated death" in human keratinocytes.

show abstract

Section: Discussionsupporting

confidence: 89%

A Previously Unreported Function of β1B Integrin Isoform in Caspase-8-Dependent Integrin-Mediated Keratinocyte Death

Lotti

Marconi

Truzzi

et al. 2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…However, caspase-8 was still slightly activated in FADDϪ/Ϫ cells, whereas the cell death induced by OSW-1 in FADDϪ/Ϫ cells was more pronounced than that in caspase-8Ϫ/Ϫ cells (Fig. 5B), suggesting that except for the Fas/FADD receptor pathway, there is another route activating caspase-8, which might be independent of the death receptor pathway (Ryu et al, 2005).…”

mentioning

confidence: 86%

Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2

Zhu

Xiong²,

Yu³

et al. 2005

Mol Pharmacol

View full text Add to dashboard Cite

OSW-1 is a new member of cholestane saponin family, which is cytotoxic against several types of malignant cells. We reported herein that OSW-1 induced apoptosis of mammalian cells in a concentration-and time-dependent manner. The drug-induced apoptosis was mediated through the mitochondrial pathway, involving the cleavage of Bcl-2. This drug-induced Bcl-2 cleavage in Chinese hamster ovary (CHO) cells could be suppressed either by dominant-negative caspase-8 or by a caspase-8 inhibitor, suggesting that the Bcl-2 cleavage is dependent on caspase-8. In contrast, the Bcl-2 cleavage was independent of caspase-3 activity. The inhibition of caspase-8 activity also resulted in the reduction of apoptotic cells, indicating that Bcl-2 cleavage induced by caspase-8 promotes the progression of apoptosis. The involvement of the caspase-8 activity in the processes of the OSW-1-induced apoptosis was further examined by using caspase-8-deficient Jurkat T cells. It was found that the caspase-8-deficient cells were resistant to OSW-1-induced Bcl-2 cleavage or apoptosis. Furthermore, the small subunit of caspase-8 was found to interact with Bcl-2 as determined by yeast two-hybrid and coimmunoprecipitation assays. Overexpression of caspase-8 small subunit reduced the cleavage of Bcl-2 and inhibited the apoptosis induced by OSW-1. Taken together, these results demonstrate that OSW-1 is capable of inducing apoptosis in mammalian cells, in which the caspase-8-dependent cleavage of Bcl-2 plays an important role.Saponins belong to a family of glycoconjugtes with a broad spectrum of biological and pharmacological activities (Hostettmann and Marson, 1995). As a new member of cholestane saponin family, OSW-1 was first isolated from the bulbs of Ornithogalum saudersiae (Kubo et al., 1992). Its total chemical synthesis was subsequently accomplished (Deng et al., 1999). It has been reported that OSW-1 was cytotoxic against several types of malignant cells at nanomolar concentrations, which are approximately 10 to 100 times more potent than those of the clinically applied anticancer agents mitomycin C and doxorubicin (Mimaki et al., 1997). Despite its highly potent antitumor activity and unique chemical structure, the molecular basis of its mechanism of action has remained elusive.Apoptosis is a universal cellular process that plays an important role in normal development as well as pathology of a number of human diseases. The resistance to apoptosis is a general feature of cancer cells. Two main pathways are involved in apoptosis. The extrinsic apoptotic pathway is activated by the ligation of death receptors, whereas the intrinsic apoptotic pathway is mediated through mitochondria (Zimmermann et al., 2001). The death receptors, such as Fas, recruit the adaptor protein FADD, which in turn recruits the proform of caspase-8. Aggregation of procaspase-8 leads to its auto-activation and subsequent activation of executioner caspases (Thorburn, 2004). The apoptotic signal can also be amplified through the mitochondria by altering its membra...

show abstract

“…Most frequently, these differences have been attributed to differences in ligand persistence, a function of ligand metabolism. For example, 7.12-dimethylbenz[a]anthracene is readily metabolized by AhR-induced monooxygenases (CYP1A1, CYP1A2, CYP1B1) and induces significant bone marrow toxicity in vivo and in vitro through apoptosis induction (Yamaguchi et al, 1997;Mann et al, 1999;Allan et al, 2003;Ryu et al, 2005;Teague et al, 2010). TCDD, which is not readily metabolized and, consequently, persists in vivo for 7-10 years, does not induce apoptosis in the bone marrow.…”

Section: Aryl Hydrocarbon Receptor As a Therapeutic Targetmentioning

confidence: 99%

Aryl Hydrocarbon Receptor Control of Adaptive Immunity

Quintana

Sherr²

2013

Pharmacol Rev

Self Cite

277

253

View full text Add to dashboard Cite

Environmental Chemical-Induced Bone Marrow B Cell Apoptosis: Death Receptor-Independent Activation of a Caspase-3 to Caspase-8 Pathway

Cited by 26 publications

References 39 publications

A Previously Unreported Function of β1B Integrin Isoform in Caspase-8-Dependent Integrin-Mediated Keratinocyte Death

A Previously Unreported Function of β1B Integrin Isoform in Caspase-8-Dependent Integrin-Mediated Keratinocyte Death

Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2

Aryl Hydrocarbon Receptor Control of Adaptive Immunity

Contact Info

Product

Resources

About