scholarly journals Necrotic Death Pathway in FAS Receptor Signaling

2000 ◽  
Vol 151 (6) ◽  
pp. 1247-1256 ◽  
Author(s):  
Hirotaka Matsumura ◽  
Yusuke Shimizu ◽  
Yoshiyuki Ohsawa ◽  
Atsuo Kawahara ◽  
Yasuo Uchiyama ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Fas Ligand ◽  
Morphological Changes ◽  
Death Receptor ◽  
Jurkat Cells ◽  
Death Process ◽  
Pyrrolidine Dithiocarbamate ◽  
Death Domain ◽  
Cell Death Process

A caspase 8–deficient subline (JB6) of human Jurkat cells can be killed by the oligomerization of Fas-associated protein with death domain (FADD). This cell death process is not accompanied by caspase activation, but by necrotic morphological changes. Here, we show that the death effector domain of FADD is responsible for the FADD-mediated necrotic pathway. This process was accompanied by a loss of mitochondrial transmembrane potential (ΔΨm), but not by the release of cytochrome c from mitochondria. Pyrrolidine dithiocarbamate, a metal chelator and antioxidant, efficiently inhibited the FADD-induced reduction of ΔΨm and necrotic cell death. When human Jurkat, or its transformants, expressing mouse Fas were treated with Fas ligand or anti–mouse Fas antibodies, the cells died, showing characteristics of apoptosis. A broad caspase inhibitor (z-VAD–fmk) blocked the apoptotic morphological changes and the release of cytochrome c. However, the cells still died, and this cell death process was accompanied by a strong reduction in ΔΨm, as well as necrotic morphological changes. The presence of z-VAD–fmk and pyrrolidine dithiocarbamate together blocked cell death, suggesting that both apoptotic and necrotic pathways can be activated through the Fas death receptor.

Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud

1993 ◽  
Vol 106 (1) ◽  
pp. 201-208 ◽  
Author(s):  
V. Garcia-Martinez ◽  
D. Macias ◽  
Y. Ganan ◽  
J.M. Garcia-Lobo ◽  
M.V. Francia ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dna Fragmentation ◽  
Limb Development ◽  
Light Transmission ◽  
Morphological Changes ◽  
Death Process ◽  
Chondrogenic Potential ◽  
Cell Death Process ◽  
Dying Cells

In this work we have attempted to characterize the programmed cell death process in the chick embryonic interdigital tissue. Interdigital cell death is a prominent phenomenon during limb development and has the role of sculpturing the digits. Morphological changes in the regressing interdigital tissue studied by light, transmission and scanning electron microscopy were correlated with the occurrence of internucleosomal DNA fragmentation, evaluated using agarose gels. Programming of the cell death process was also analyzed by testing the chondrogenic potential of the interdigital mesenchyme, in high density cultures. Our results reveal a progressive loss of the chondrogenic potential of the interdigital mesenchyme, detectable 36 hours before the onset of the degenerative process. Internucleosomal DNA fragmentation was only detected concomitant with the appearance of cells dying with the morphology of apoptosis, but unspecific DNA fragmentation was also present at the same time. This unspecific DNA fragmentation was explained by a precocious activation of the phagocytic removal of the dying cells, confirmed in the tissue sections. From our observations it is suggested that programming of cell death involves changes before endonuclease activation. Further, cell surface changes involved in the phagocytic uptake of the dying cells appear to be as precocious as endonuclease activation.

Hypoxia induces apoptosis via two independent pathways in Jurkat cells: differential regulation by glucose

2001 ◽  
Vol 281 (5) ◽  
pp. C1596-C1603 ◽  
Author(s):  
Ricky Malhotra ◽  
Zhiwu Lin ◽  
Claudius Vincenz ◽  
Frank C. Brosius
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Death Receptor ◽  
Jurkat Cells ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Extracellular Glucose ◽  
Uptake And Metabolism

Glucose uptake and metabolism inhibit hypoxia-induced apoptosis in a variety of cell types, but the underlying molecular mechanisms remain poorly understood. In the present study, we explore hypoxia-mediated cell death pathways in Jurkat cells in the presence and absence of extracellular glucose. In the absence of extracellular glucose, hypoxia caused cytochrome c release, caspase 3 and poly(ADP-ribose)polymerase cleavage, and DNA fragmentation; this apoptotic response was blocked by the caspase 9 inhibitor z-LEHD-FMK. The presence of extracellular glucose during hypoxia prevented cytochrome c release and activation of caspase 9 but did not prevent apoptosis in Jurkat cells. In these conditions, overexpression of the caspase 8 inhibitor v-FLIP prevented hypoxia-mediated cell death. Thus hypoxia can stimulate two apoptotic pathways in Jurkat cells, one dependent on cytochrome c release from mitochondria that is prevented by glucose uptake and metabolism, and the other independent of cytochrome c release and resulting from activation of the death receptor pathway, which is accelerated by glucose uptake and metabolism.

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.

scholarly journals Correction: PML induces a novel caspase-independent cell death process

10.1038/8706 ◽  
1999 ◽  
Vol 22 (1) ◽  
pp. 115-115 ◽  
Author(s):  
Fredérique Quignon
Keyword(s):  
Cell Death ◽  
Death Process ◽  
Cell Death Process

scholarly journals Death Receptor-Induced Activation of Initiator Caspase 8 Is Antagonized by Serine/Threonine Kinase PAK4

2003 ◽  
Vol 23 (21) ◽  
pp. 7838-7848 ◽  
Author(s):  
Nerina Gnesutta ◽  
Audrey Minden
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Intracellular Signaling ◽  
Death Receptor ◽  
Caspase 8 ◽  
Death Domain ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Different Types ◽  
Promote Cell Survival

ABSTRACT Normal cell growth requires a precisely controlled balance between cell death and survival. This involves activation of different types of intracellular signaling cascades within the cell. While some types of signaling proteins regulate apoptosis, or programmed cell death, other proteins within the cell can promote survival. The serine/threonine kinase PAK4 can protect cells from apoptosis in response to several different types of stimuli. As is the case for other members of the p21-activated kinase (PAK) family, one way that PAK4 may promote cell survival is by phosphorylating and thereby inhibiting the proapoptotic protein Bad. This leads in turn to the inhibition of effector caspases such as caspase 3. Here we show that in response to cytokines which activate death domain-containing receptors, such as the tumor necrosis factor and Fas receptors, PAK4 can inhibit the death signal by a different mechanism. Under these conditions, PAK4 inhibits apoptosis early in the caspase cascade, antagonizing the activation of initiator caspase 8. This inhibition, which does not require PAK4's kinase activity, may involve inhibition of caspase 8 recruitment to the death domain receptors. This role in regulating initiator caspases is an entirely novel role for the PAK proteins and suggests a new mechanism by which these proteins promote cell survival.

scholarly journals Production of Prodiginines Is Part of a Programmed Cell Death Process in Streptomyces coelicolor

2018 ◽  
Vol 9 ◽  
Author(s):  
Elodie Tenconi ◽  
Matthew F. Traxler ◽  
Charline Hoebreck ◽  
Gilles P. van Wezel ◽  
Sébastien Rigali
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Streptomyces Coelicolor ◽  
Death Process ◽  
Cell Death Process

Characterization of cell death process in plant cells induced by hipoxia and anoxia

2000 ◽  
Vol 28 (5) ◽  
pp. A372-A372
Author(s):  
E. N. Baranova ◽  
N. V. Kononenko ◽  
T. V. Bragina ◽  
G. M. Grineva ◽  
T. P. Astafurova ◽  
...  
Keyword(s):  
Cell Death ◽  
Plant Cells ◽  
Death Process ◽  
Cell Death Process

scholarly journals Oxidative Stress in Cell Death and Cardiovascular Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Xu ◽  
Wei Ding ◽  
Xiaoyu Ji ◽  
Xiang Ao ◽  
Ying Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Death Process ◽  
Ros Production ◽  
Disease Treatment ◽  
Physiological Conditions ◽  
Intracellular Ros ◽  
Cell Death Process ◽  
Molecular Components ◽  
Multiple Signaling

ROS functions as a second messenger and modulates multiple signaling pathways under the physiological conditions. However, excessive intracellular ROS causes damage to the molecular components of the cell, which promotes the pathogenesis of various human diseases. Cardiovascular diseases are serious threats to human health with extremely high rates of morbidity and mortality. Dysregulation of cell death promotes the pathogenesis of cardiovascular diseases and is the clinical target during the disease treatment. Numerous studies show that ROS production is closely linked to the cell death process and promotes the occurrence and development of the cardiovascular diseases. In this review, we summarize the regulation of intracellular ROS, the roles of ROS played in the development of cardiovascular diseases, and the programmed cell death induced by intracellular ROS. We also focus on anti-ROS system and the potential application of anti-ROS strategy in the treatment of cardiovascular diseases.

Sign in / Sign up

Export Citation Format

Share Document