Role of the Fas/Fas Ligand death receptor pathway in ginseng saponin metabolite-induced apoptosis in hepg2 cells

2004 ◽  
Vol 27 (4) ◽  
pp. 402-406 ◽  
Author(s):  
Seon-Hee Oh ◽  
Hu-Quan Yin ◽  
Byung-Hoon Lee
Keyword(s):  
Hepg2 Cells ◽  
Fas Ligand ◽  
Death Receptor ◽  
Death Receptor Pathway ◽  
Ginseng Saponin ◽  
Induced Apoptosis

scholarly journals The Fas/Fas Ligand Death Receptor Pathway Contributes to Phenylalanine-Induced Apoptosis in Cortical Neurons

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71553 ◽  
Author(s):  
Xiaodong Huang ◽  
Zhaohui Lu ◽  
Zhongwei Lv ◽  
Tingting Yu ◽  
Peirong Yang ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Fas Ligand ◽  
Death Receptor ◽  
Death Receptor Pathway ◽  
Induced Apoptosis

scholarly journals sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2177
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Dmytro Petukhov ◽  
Ronit Ahdut-HaCohen ◽  
Mark Richter-Dayan ◽  
Raphael Breuer
Keyword(s):  
Cell Death ◽  
Lung Disease ◽  
Fas Ligand ◽  
Death Receptor ◽  
Mesenchymal Cells ◽  
Soluble Form ◽  
Cell Accumulation ◽  
Key Factor ◽  
Aged Subjects

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.

Role of S-adenosylhomocysteine hydrolase in adenosine-induced apoptosis in HepG2 cells

2007 ◽  
Vol 313 (2) ◽  
pp. 264-283 ◽  
Author(s):  
Marina Hermes ◽  
Hartmut Osswald ◽  
Doris Kloor
Keyword(s):  
Hepg2 Cells ◽  
Adenosylhomocysteine Hydrolase ◽  
Induced Apoptosis

The Protective Role of Selenium Against AFB1-Induced Liver Apoptosis by Death Receptor Pathway in Broilers

2019 ◽  
Vol 191 (2) ◽  
pp. 453-463 ◽  
Author(s):  
Bangyuan Wu ◽  
Muhammad Jameel Mughal ◽  
Jing Fang ◽  
Xi Peng
Keyword(s):  
Death Receptor ◽  
Protective Role ◽  
Death Receptor Pathway

Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human liver HepG2 and L02 cells

2018 ◽  
Vol 37 (12) ◽  
pp. 1293-1309 ◽  
Author(s):  
Y Xue ◽  
J Wang ◽  
Y Huang ◽  
X Gao ◽  
L Kong ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Hepatoma Cell ◽  
Death Receptor ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Death Receptor Pathway ◽  
L02 Cells

Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20–160 μg mL−1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.

Acquired Resistance to Tumor Necrosis Factor-Related Apoptosis- Inducing Ligand (TRAIL): Histone Deacetylase Inhibitors Resensitize TRAIL-Resistant Jurkat Acute Lymphocytic Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5032-5032
Author(s):  
Pavel Klener ◽  
Jan Molinsky ◽  
Tereza Simonova ◽  
Emanuel Necas ◽  
Ladislav Andera ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Fas Ligand ◽  
Death Receptor ◽  
Lymphocytic Leukemia ◽  
Jurkat Cells ◽  
Tnf Alpha ◽  
Apoptotic Pathway ◽  
Induced Apoptosis ◽  
Disc Formation

Abstract Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a death-ligand from the TNF family. TRAIL induces programmed cell death by the cell-extrinsic p53-independent apoptotic pathway. A potential of TRAIL as cancer-specific therapeutic agent has been proposed and is preclinically and clinically tested. Development of TRAIL-resistant clones in the TRAIL-sensitive tumor cells may be a serious complication of TRAIL based cancer therapy. Jurkat acute lymphocytic leukemia cells are sensitive to TRAIL-induced apoptosis, as well as other apoptosis inducing ligands from TNF family, Fas and TNF-alpha. Jurkat cells express only one of the four receptors for TRAIL, death receptor 5 (DR5). Prolonged exposure of TRAIL-sensitive Jurkat cells to recombinant soluble TRAIL (1000 ng/mL) resulted in the establishment of three TRAIL-resistant (TR) Jurkat cell subclones, Jurkat TR1, TR2, and TR3. The Jurkat TR subclones were also resistant to TNF-alpha and Fas ligand, suggesting disruption of the extrinsic apoptotic pathway. TRAIL-resistant subclone TR1, but not TR2 and TR3, demonstrated decreased susceptibility to undergo apoptosis in response to histone-deacetylase inhibitors, valproic acid (VA), sodium butyrate (SB) and suberoylanilide hydroxamic acid (SAHA) and was resistant to fludarabine. Flow cytometry analysis showed Jurkat TR subclones had unchanged expression of cell surface death receptor DR5, Fas, and receptors for TNF-alpha, TNF-R1 and TNF-R2, compared to TRAIL-sensitive Jurkat cells. Analysis of death-inducing signaling complex (DISC) formation by immunoprecipitation (anti-TRAIL, anti-DR5) and subsequent western blotting (anti-caspase 8, anti-FADD) clearly demonstrated that the DISC formation in response to TRAIL binding to DR5 was significantly decreased in subclones TR2 and TR3, but remained unchanged in subclone TR1 compared to TRAIL-sensitive Jurkat cells. To gain further insight into potential molecular aletarations associated with acquired TRAIL resistance of Jurkat subclones, we measured gene expression of several key apoptotic regulators, including receptors for TRAIL, cFLIP, BCL2 family, IAP family, HSP family members in TRAIL-resistant and TRAIL-sensitive Jurkat cells and did not detect any significant (>2-fold) change. These results suggest acquired TRAIL resistance of Jurkat cells might be mediated by changes on the protein rather than mRNA level. We analyzed whether the TRAIL-resistant Jurkat cells could be resensitized to TRAIL-induced apoptosis by pretreatment with diverse inhibitors of important prosurvival pathways, including inhibitors of proteosynthesis (cycloheximid), inhibitors of transcription (actinomycin D), NFkB inhibitors (bortezomib, SN-50), PI3K-Akt-mTOR inhibitors (rapamycine, LY294002, Hsp90 inhibitor (17-AAG), cyclin-dependent kinase inhibitors (roscovitine), casein kinase II inhibitors (DRB), or histone deacetylase inhibitors (HDACi: SAHA, VA, SB). Pretreatment with HDAC inhibitors for 12 hour was able to resensitize all three TRAIL-resistant Jurkat subclones to TRAIL-induced apoptosis. The percentage of apoptotic cells of HDACi-pretreated subclones was 70–95% 24 h after the exposure to TRAIL compared to 5–15% apoptosis for HDACi-untreated TRAIL-exposed controls, and to 10–15% apoptosis for HDACi-treated TRAIL unexposed controls. We established TRAIL-resistant subclones from the original TRAIL-sensitive Jurkat cells. Acquired resistance to TRAIL was not mediated by downregulation of TRAIL death receptor DR5 and was associated with (cross)resistance to TNFa and Fas ligand, suggesting disruption of cell-extrinsic apoptotic pathway. We assume diverse molecular mechanisms were involved in the development of TRAIL-resistant subclones upon exposure to TRAIL, as exemplified by disrupted formation of DISC in case of subclones TR2 and TR3 and normal DISC formation and fludarabine resistance in subclone TR1, suggesting deregulated apoptotic pathway downstream of DISC. Finally, we observed that HDACi resensitized the TRAIL-resistant subclones to TRAIL. The results provide substantiation for combinatorial approaches in the potential TRAIL-based therapies of hematological malignancies.

Apoptotic Role of Fas/Fas Ligand System in the Regulation of Erythropoiesis

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 796-803 ◽  
Author(s):  
R. De Maria ◽  
U. Testa ◽  
L. Luchetti ◽  
A. Zeuner ◽  
G. Stassi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fas Ligand ◽  
Control Mechanism ◽  
Erythroid Differentiation ◽  
Dependent Manner ◽  
Normal Bone ◽  
In Vivo Analysis ◽  
Induced Apoptosis

The possible involvement of Fas and Fas ligand (FasL) in the regulation of erythropoiesis was evaluated. Immunohistochemistry of normal bone marrow specimens revealed that several immature erythroblasts undergo apoptosis in vivo. Analysis of bone marrow erythroblasts and purified progenitors undergoing unilineage erythroid differentiation showed that Fas is rapidly upregulated in early erythroblasts and expressed at high levels through terminal maturation. However, Fas crosslinking was effective only in less mature erythroblasts, particularly at basophilic level, where it induced apoptosis antagonized by high levels of erythropoietin (Epo). In contrast, FasL was selectively induced in late differentiating Fas-insensitive erythroblasts, mostly at the orthochromatic stage. FasL is functional in mature erythroblasts, as it was able to kill Fas-sensitive lymphoblast targets in a Fas-dependent manner. Importantly, FasL-bearing mature erythroblasts displayed a Fas-based cytotoxicity against immature erythroblasts, which was abrogated by high levels of Epo. These findings suggest the existence of a negative regulatory feedback between mature and immature erythroid cells, whereby the former cell population might exert a cytotoxic effect on the latter one in the erythroblastic island. Hypothetically, this negative feedback operates at low Epo levels to moderate the erythropoietic rate; however, it is gradually inhibited at increasing Epo concentrations coupled with enhanced erythrocyte production. Thus, the interaction of Fas and FasL may represent an apoptotic control mechanism for erythropoiesis, contributing to the regulation of red blood cell homeostasis.

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.

scholarly journals Role of reactive oxygen species (ROS) and JNKs in selenite-induced apoptosis in HepG2 cells

2008 ◽  
Vol 7 (5) ◽  
pp. 697-698 ◽  
Author(s):  
Durga P. Cherukuri ◽  
Mark A. Nelson, V
Keyword(s):  
Reactive Oxygen Species ◽  
Hepg2 Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Induced Apoptosis
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