scholarly journals Important Role of β1-Integrin in Fucoidan-Induced Apoptosis via Caspase-8 Activation

2012 ◽  
Vol 76 (6) ◽  
pp. 1163-1168 ◽  
Author(s):  
Yumi YAMASAKI ◽  
Masao YAMASAKI ◽  
Hirofumi TACHIBANA ◽  
Koji YAMADA
Keyword(s):  
Caspase 8 ◽  
Induced Apoptosis

scholarly journals Differential role of caspase-8 and BID activation during radiation- and CD95-induced apoptosis

Oncogene ◽  
2000 ◽  
Vol 19 (9) ◽  
pp. 1181-1190 ◽  
Author(s):  
C Belka ◽  
J Rudner ◽  
S Wesselborg ◽  
A Stepczynska ◽  
P Marini ◽  
...  
Keyword(s):  
Caspase 8 ◽  
Induced Apoptosis

scholarly journals Model-based dissection of CD95 signaling dynamics reveals both a pro- and antiapoptotic role of c-FLIPL

2010 ◽  
Vol 190 (3) ◽  
pp. 377-389 ◽  
Author(s):  
Nicolai Fricker ◽  
Joel Beaudouin ◽  
Petra Richter ◽  
Roland Eils ◽  
Peter H. Krammer ◽  
...  
Keyword(s):  
Death Receptor ◽  
Caspase 8 ◽  
Converting Enzyme ◽  
Receptor Stimulation ◽  
Western Blots ◽  
Antiapoptotic Protein ◽  
Signaling Complex ◽  
Signaling Dynamics ◽  
Induced Apoptosis

Cellular FADD-like interleukin-1β–converting enzyme inhibitory proteins (c-FLIPs; isoforms c-FLIP long [c-FLIPL], c-FLIP short [c-FLIPS], and c-FLIP Raji [c-FLIPR]) regulate caspase-8 activation and death receptor (DR)–induced apoptosis. In this study, using a combination of mathematical modeling, imaging, and quantitative Western blots, we present a new mathematical model describing caspase-8 activation in quantitative terms, which highlights the influence of c-FLIP proteins on this process directly at the CD95 death-inducing signaling complex. We quantitatively define how the stoichiometry of c-FLIP proteins determines sensitivity toward CD95-induced apoptosis. We show that c-FLIPL has a proapoptotic role only upon moderate expression in combination with strong receptor stimulation or in the presence of high amounts of one of the short c-FLIP isoforms, c-FLIPS or c-FLIPR. Our findings resolve the present controversial discussion on the function of c-FLIPL as a pro- or antiapoptotic protein in DR-mediated apoptosis and are important for understanding the regulation of CD95-induced apoptosis, where subtle differences in c-FLIP concentrations determine life or death of the cells.

MiR-21 regulates the apoptosis of keloid fibroblasts by caspase-8 and the mitochondria-mediated apoptotic signaling pathway via targeting FasL

2018 ◽  
Vol 96 (5) ◽  
pp. 548-555 ◽  
Author(s):  
Ying Liu ◽  
Lihong Ren ◽  
Wenjing Liu ◽  
Zhibo Xiao
Keyword(s):  
Signaling Pathway ◽  
Mitochondrial Membrane ◽  
Caspase 8 ◽  
Apoptotic Signaling ◽  
Over Expression ◽  
Mitochondrial Ros ◽  
Proliferation And Apoptosis ◽  
Induced Apoptosis ◽  
Keloid Fibroblasts

MicroRNA-21 (miR-21) has been found to be upregulated in keloid tissue and to affect the proliferation and apoptosis of keloid fibroblasts; however, the possible mechanisms remain unclear. In this study, we aimed to evaluate the role of miR-21 in FasL-induced caspase-8 activation and the mitochondria-mediated apoptotic signaling pathway in keloid fibroblasts. Our study found that the protein level of FasL was decreased by miR-21 over-expression, while being enhanced by miR-21 inhibition in keloid fibroblasts. Subsequently, the mitochondria-mediated apoptosis of keloid fibroblasts was restrained by miR-21 over-expression, as evidenced by enhanced mitochondrial membrane potential and decreased production of mitochondrial ROS. Moreover, over-expression of miR-21 inhibited the activation of the caspase-8 and the mitochondria-mediated apoptotic signaling pathway. As expected, inhibition of miR-21 had the opposite effects. Finally, silencing of FasL suppressed miR-21 inhibition-induced apoptosis by inactivation of caspase-8 and the mitochondria-mediated apoptotic signaling pathway, which was comparable to Z-IETD-FMK, a caspase-8 inhibitor. Taken together, these results suggest that miR-21 regulates the apoptosis of keloid fibroblasts via targeting FasL, and caspase-8 and the mitochondria-mediated apoptotic signaling pathway is involved in this process. Our findings provide evidence that miR-21 may be considered to be a therapeutic target for keloids.

scholarly journals Balance between short and long isoforms of cFLIP regulates Fas-mediated apoptosis in vivo

2016 ◽  
Vol 113 (6) ◽  
pp. 1606-1611 ◽  
Author(s):  
Daniel R. Ram ◽  
Vladimir Ilyukha ◽  
Tatyana Volkova ◽  
Anton Buzdin ◽  
Albert Tai ◽  
...  
Keyword(s):  
Splice Variants ◽  
Death Receptor ◽  
Liver Cells ◽  
Caspase 8 ◽  
Differential Splicing ◽  
Genome Wide ◽  
In The Wild ◽  
Induced Apoptosis

cFLIP, an inhibitor of apoptosis, is a crucial regulator of cellular death by apoptosis and necroptosis; its importance in development is exemplified by the embryonic lethality in cFLIP–deficient animals. A homolog of caspase 8 (CASP8), cFLIP exists in two main isoforms: cFLIPL (long) and cFLIPR (short). Although both splice variants regulate death receptor (DR)-induced apoptosis by CASP8, the specific role of each isoform is poorly understood. Here, we report a previously unidentified model of resistance to Fas receptor-mediated liver failure in the wild-derived MSM strain, compared with susceptibility in C57BL/6 (B6) mice. Linkage analysis in F2 intercross (B6 x MSM) progeny identified several MSM loci controlling resistance to Fas-mediated death, including the caspase 8- and FADD-like apoptosis regulator (Cflar) locus encoding cFLIP. Furthermore, we identified a 21-bp insertion in the 3′ UTR of the fifth exon of Cflar in MSM that influences differential splicing of cFLIP mRNA. Intriguingly, we observed that MSM liver cells predominantly express the FLIPL variant, in contrast to B6 liver cells, which have higher levels of cFLIPR. In keeping with this finding, genome-wide RNA sequencing revealed a relative abundance of FLIPL transcripts in MSM hepatocytes whereas B6 liver cells had significantly more FLIPR mRNA. Importantly, we show that, in the MSM liver, CASP8 is present exclusively as its cleaved p43 product, bound to cFLIPL. Because of partial enzymatic activity of the heterodimer, it might prevent necroptosis. On the other hand, it prevents cleavage of CASP8 to p10/20 necessary for cleavage of caspase 3 and, thus, apoptosis induction. Therefore, MSM hepatocytes are predisposed for protection from DR-mediated cell death.

Heterogeneous Role of Caspase-8 in Fenretinide-Induced Apoptosis in Epithelial Ovarian Carcinoma Cell Lines

2003 ◽  
Vol 64 (6) ◽  
pp. 1434-1443 ◽  
Author(s):  
Kimberly R. Kalli ◽  
Kathryn E. Devine ◽  
Myles C. Cabot ◽  
Christina R. Arnt ◽  
Michael P. Heldebrant ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Epithelial Ovarian Carcinoma ◽  
Caspase 8 ◽  
Carcinoma Cell Lines ◽  
Induced Apoptosis

A Crucial Role of Caspase 3 and Caspase 8 in Paclitaxel-Induced Apoptosis

1999 ◽  
Vol 2 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Haruki Oyaizu ◽  
Yasushi Adachi ◽  
Shigeru Taketani ◽  
Rikio Tokunaga ◽  
Shirou Fukuhara ◽  
...  
Keyword(s):  
Crucial Role ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Induced Apoptosis

scholarly journals Apoptotic Response of Chang Cells to Infection with Pseudomonas aeruginosa Strains PAK and PAO-I: Molecular Ordering of the Apoptosis Signaling Cascade and Role of Type IV Pili

2003 ◽  
Vol 71 (5) ◽  
pp. 2665-2673 ◽  
Author(s):  
Verena Jendrossek ◽  
Sophie Fillon ◽  
Claus Belka ◽  
Ilka Müller ◽  
Beatrice Puttkammer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Host Cells ◽  
Caspase 8 ◽  
Mitochondrial Alterations ◽  
Human Epithelial Cells ◽  
Molecular Ordering ◽  
Induced Apoptosis ◽  
Chang Cells

ABSTRACT Pseudomonas aeruginosa is a gram-negative facultative opportunistic pathogen associated with severe infections in immunocompromised hosts and in patients with cystic fibrosis. P. aeruginosa strains show divergent pathogenicity in vivo and trigger apoptosis of and/or are internalized into human host cells. In the present study, we studied the molecular ordering of apoptosis signaling upon infection of human conjunctiva epithelial Chang cells with P. aeruginosa PAK as well as the role of bacterial pili in the response to the infection. Our results show that CD95 up-regulation is followed by early activation of caspase-8 and -3 and cleavage of the caspase-3 substrate poly(ADP-ribose) polymerase. The data also demonstrate release of apoptosis inducing factor into the cytosol of infected cells. Induction of mitochondrial alterations, i.e., mitochondrial depolarization and release of cytochrome c, as well as cleavage of caspase-9, -7, and -1 occurred only at later time points. In addition, our results demonstrate that pili are required for P. aeruginosa-induced apoptosis of human epithelial cells. While the two piliated P. aeruginosa strains, PAO-I and PAK, induced apoptosis of Chang cells within 3 h of infection, the pilus-deficient P. aeruginosa mutants PAKΔpilA and PAKΔpilAΔall were without effect. The pilus-deficient mutants failed to induce a significant up-regulation of CD95 on the cell surface and to trigger mitochondrial alterations or activation of caspase-8, -3, and -7. In addition, only the piliated wild-type strains induced caspase-1-mediated activation of interleukin-1β. Thus, pili are necessary for distinct infection-induced cellular responses of human epithelial cells.

Mechanism of 2′,3′-dimethoxyflavanone-induced apoptosis in breast cancer stem cells: Role of ubiquitination of caspase-8 and LC3

2014 ◽  
Vol 562 ◽  
pp. 92-102 ◽  
Author(s):  
Thao Anh Tran ◽  
Kwang Seok Ahn ◽  
Yeon Woo Song ◽  
Jeong Yong Moon ◽  
Moonjae Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Caspase 8 ◽  
Breast Cancer Stem Cells ◽  
Induced Apoptosis

The IKK2/NF-κB pathway suppresses MYC-induced lymphomagenesis

Blood ◽  
2009 ◽  
Vol 114 (12) ◽  
pp. 2448-2458 ◽  
Author(s):  
Kay Klapproth ◽  
Sandrine Sander ◽  
Dragan Marinkovic ◽  
Bernd Baumann ◽  
Thomas Wirth
Keyword(s):  
Cell Death ◽  
Burkitt Lymphoma ◽  
Selective Advantage ◽  
Hematologic Malignancies ◽  
Caspase 8 ◽  
Lymphoma Cells ◽  
Murine Lymphoma ◽  
Induced Apoptosis

Abstract Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematologic malignancies, enhanced NF-κB exerts prosurvival functions. Here we investigated the role of NF-κB in mouse and human c-MYC–transformed lymphomas. The NF-κB pathway is extinguished in murine lymphoma cells, and extrinsic stimuli typically inducing NF-κB activity fail to activate this pathway. Genetic activation of the NF-κB pathway induces apoptosis in these cells, whereas inhibition of NF-κB by an IκBα superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt lymphoma cells we find that NF-κB activation induces apoptosis. NF-κB up-regulates Fas and predisposes to Fas-induced cell death, which is caspase-8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-κB–induced apoptosis, and persistent inactivity of NF-κB signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC-driven lymphoma cells are reversed by activation of NF-κB. Our observations provide a molecular explanation for the described absence of the NF-κB signaling in Burkitt lymphoma and question the applicability of NF-κB inhibitors as candidates for treatment of this cancer.

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