scholarly journals Induction of Mitochondrial Alternative Oxidase in Response to a Cell Signal Pathway Down-Regulating the Cytochrome Pathway Prevents Programmed Cell Death

2002 ◽  
Vol 129 (4) ◽  
pp. 1829-1842 ◽  
Author(s):  
Greg C. Vanlerberghe ◽  
Christine A. Robson ◽  
Justine Y.H. Yip
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Alternative Oxidase ◽  
Signal Pathway ◽  
Cell Signal ◽  
Cytochrome Pathway ◽  
A Cell

scholarly journals Macrophage Autophagy and Oxidative Stress: An Ultrastructural and Immunoelectron Microscopical Study

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Ida Perrotta ◽  
Valentina Carito ◽  
Emilio Russo ◽  
Sandro Tripepi ◽  
Saveria Aquila ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Defense Mechanisms ◽  
Ultrastructural Localization ◽  
Microscopical Study ◽  
Beclin 1 ◽  
Cell Organelles ◽  
A Cell ◽  
First Time

The word autophagy broadly refers to the cellular catabolic processes that lead to the removal of damaged cytosolic proteins or cell organelles through lysosomes. Although autophagy is often observed during programmed cell death, it may also serve as a cell survival mechanism. Accumulation of reactive oxygen species within tissues and cells induces various defense mechanisms or programmed cell death. It has been shown that, besides inducing apoptosis, oxidative stress can also induce autophagy. To date, however, the regulation of autophagy in response to oxidative stress remains largely elusive and poorly understood. Therefore, the present study was designed to examine the ratio between oxidative stress and autophagy in macrophages after oxidant exposure (AAPH) and to investigate the ultrastructural localization of beclin-1, a protein essential for autophagy, under basal and stressful conditions. Our data provide evidence that oxidative stress induces autophagy in macrophages. We demonstrate, for the first time by immunoelectron microscopy, the subcellular localization of beclin-1 in autophagic cells.

scholarly journals Long-term depression: a cell biological view

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130138 ◽  
Author(s):  
Morgan Sheng ◽  
Ali Ertürk
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dendritic Spines ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Long Term Depression ◽  
A Cell ◽  
Biological Programme

Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.

scholarly journals Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death.

1996 ◽  
Vol 133 (5) ◽  
pp. 1041-1051 ◽  
Author(s):  
M D Jacobsen ◽  
M Weil ◽  
M C Raff
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mammalian Cell ◽  
Mammalian Cells ◽  
Apoptotic Cell ◽  
Interleukin 1 ◽  
Cell Types ◽  
Cysteine Proteases ◽  
A Cell ◽  
Bona Fide

In the accompanying paper by Weil et al. (1996) we show that staurosporine (STS), in the presence of cycloheximide (CHX) to inhibit protein synthesis, induces apoptotic cell death in a large variety of nucleated mammalian cell types, suggesting that all nucleated mammalian cells constitutively express all of the proteins required to undergo programmed cell death (PCD). The reliability of that conclusion depends on the evidence that STS-induced, and (STS + CHS)-induced, cell deaths are bona fide examples of PCD. There is rapidly accumulating evidence that some members of the Ced-3/Interleukin-1 beta converting enzyme (ICE) family of cysteine proteases are part of the basic machinery of PCD. Here we show that Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a cell-permeable, irreversible, tripeptide inhibitor of some of these proteases, suppresses STS-induced and (STS + CHX)-induced cell death in a wide variety of mammalian cell types, including anucleate cytoplasts, providing strong evidence that these are all bona fide examples of PCD. We show that the Ced-3/ICE family member CPP32 becomes activated in STS-induced PCD, and that Bcl-2 inhibits this activation. Most important, we show that, in some cells at least, one or more CPP32-family members, but not ICE itself, is required for STS-induced PCD. Finally, we show that zVAD-fmk suppresses PCD in the interdigital webs in developing mouse paws and blocks the removal of web tissue during digit development, suggesting that this inhibition will be a useful tool for investigating the roles of PCD in various developmental processes.

Proapoptotic Bid Preserves HSC Function through Restraint of Necroptosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 251-251
Author(s):  
Patrice N. Wagner ◽  
Qiong Shi ◽  
Yuri D. Fedoriw ◽  
Sandra S. Zinkel
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Model ◽  
Caspase 3 ◽  
Bone Marrow Failure ◽  
Marrow Cell ◽  
Caspase 8 ◽  
Complex Ii ◽  
A Cell

Abstract Multicellular organisms remove damaged or superfluous cells through a highly regulated cellular process known as programmed cell death. There are two main forms of programmed cell death, apoptosis and necrosis. Necrosis (necroptosis) previously thought to be an unregulated death pathway was recently found to be highly regulated. The manner by which a cell dies has important implications. In apoptotic cell death, caspases digest the cell to cause implosion in an immunologically silent process. In necroptotic cell death, increased Rip kinase signaling effects rupture of the plasma membrane, cellular explosion, and the activation of an inflammatory response. Death receptors, such as the TNFα receptor, can activate either apoptotic or necroptotic death. The upstream activators and transducers including Caspase-8, Rip1, and Fadd, are common to both forms of cell death. Interestingly, Caspase-8 and c-FlipL, a caspase homolog, were recently shown to inhibit the necrotic pathway during embryonic development through the formation of a catalytically active complex. The BH3-only Bcl-2 family member, Bid is one of the strongest substrates of Caspase-8, placing it at the interface of the apoptotic and necroptotic pathways, and in position to mediate cell death fate. The role of apoptosis in hematopoietic homeostasis has been well characterized. We developed a mouse model of unrestrained necroptosis in order to determine how unrestrained necroptosis impacts hematopoietic homeostasis and bone marrow function. To do this we generated a mouse model in which apoptosis is prevented by the deletion of the pro-apoptotic effectors Bax and Bak. We further deleted the upstream activator Bid (VavBaxBakBid TKO mice). Surprisingly, these mice die of bone marrow failure due to unrestrained necroptotic cell death. TKO bone marrow displays necroptotic cells by electron microscopy, and markedly increased Rip1 expression by immunofluorescence. TKO mice die of bone marrow failure with marked myeloid dysplasia between the age of 3 and 12 months, and a small number develop leukemia, a phenotype that closely resembles MDS. Further analysis revealed expansion and increased BrdU incorporation of the SLAM-HSC population, consistent with increased HSC proliferation in response to death of more mature cells. To assess function of these HSCs, we performed competitive reconstitution assays. TKO bone marrow initially outcompetes WT bone marrow, but the mice eventually succumb to bone marrow failure beginning at 5 months post–transplantation, despite the presence of ~10-15% wild type bone marrow. These results demonstrate that increased necroptotic signaling results in a cell autonomous stem cell defect. In addition, the presence of necroptotic bone marrow also kills normal HSCs in a non cell-autonomous manner, due to a feed-forward inflammatory process. To further characterize how necroptotic cell death is regulated, we developed myeloid progenitor cell lines (MPCs) from the bone marrow of WT, Bid KO, BaxBak DKO, and BaxBakBid TKO mice to facilitate biochemical and mechanistic studies. Our studies demonstrated increased activation (phosphorylation) and markedly increased levels of Rip1 in the pronecrotic complex (Complex II) with Rip3, Caspase-8, and Fadd in our TKO MPCs following LPS treatment. This association of Rip1 with Complex II is abrogated by reintroduction of Bid by retrovirus into TKO MPCs, demonstrating that Bid inhibits Rip1 association with complex II, suggesting that Bid is a key factor that determines cell death fate. Increased bone marrow cell death is well documented in MDS. To determine if necroptosis plays a role in this bone marrow cell death, we evaluated RIP1 and Caspase 3 expression in 17 human MDS samples. Remarkably, we found increased RIP1 expression, but not activated caspase 3 in bone marrow samples from patients with the RCMD, RAEB-1, and RAEB-2 subtype of MDS, but not in 4 control bone marrow samples (normal lymphoma staging marrows). Our study thus demonstrates that increased necroptosis signaling can result in bone marrow failure with dysplasia, and that necroptotic cell death signaling is increased in bone marrow from MDS patients, highlighting the potential importance of this targetable signaling pathway in bone marrow failure disorders such as MDS. Disclosures No relevant conflicts of interest to declare.

Post-embryonic development in the ventral cord of Caenorhabditis elegans

1976 ◽  
Vol 275 (938) ◽  
pp. 287-297 ◽  
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Programmed Cell Death ◽  
Embryonic Development ◽  
Nerve Cells ◽  
Ventral Cord ◽  
Larval Moult ◽  
A Cell

56 nerve cells are added to the ventral cord and associated ganglia of Caenorhabditis elegans at about the time of the first larval moult. These cells are produced by the uniform division of 13 neuroblasts followed by a defined pattern of cell deaths. Comparison with the data in the previous paper suggests that there is a relationship between the ancestry of a cell and its function. The significance of programmed cell death is discussed.

scholarly journals Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis

2016 ◽  
Vol 113 (10) ◽  
pp. 2720-2725 ◽  
Author(s):  
Asen Daskalov ◽  
Birgit Habenstein ◽  
Raimon Sabaté ◽  
Mélanie Berbon ◽  
Denis Martinez ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Amyloid Fibrils ◽  
Evolutionary Relationship ◽  
X Ray Diffraction ◽  
Nmr Studies ◽  
Gene Encoding ◽  
Prion Propagation ◽  
A Cell ◽  
New Type

Recent findings have revealed the role of prion-like mechanisms in the control of host defense and programmed cell death cascades. In fungi, HET-S, a cell death-inducing protein containing a HeLo pore-forming domain, is activated through amyloid templating by a Nod-like receptor (NLR). Here we characterize the HELLP protein behaving analogously to HET-S and bearing a new type of N-terminal cell death-inducing domain termed HeLo-like (HELL) and a C-terminal regulatory amyloid motif known as PP. The gene encoding HELLP is part of a three-gene cluster also encoding a lipase (SBP) and a Nod-like receptor, both of which display the PP motif. The PP motif is similar to the RHIM amyloid motif directing formation of the RIP1/RIP3 necrosome in humans. The C-terminal region of HELLP, HELLP(215-278), encompassing the motif, allows prion propagation and assembles into amyloid fibrils, as demonstrated by X-ray diffraction and FTIR analyses. Solid-state NMR studies reveal a well-ordered local structure of the amyloid core residues and a primary sequence that is almost entirely arranged in a rigid conformation, and confirm a β-sheet structure in an assigned stretch of three amino acids. HELLP is activated by amyloid templating and displays membrane-targeting and cell death-inducing activity. HELLP targets the SBP lipase to the membrane, suggesting a synergy between HELLP and SBP in membrane dismantling. Remarkably, the HeLo-like domain of HELLP is homologous to the pore-forming domain of MLKL, the cell death-execution protein in necroptosis, revealing a transkingdom evolutionary relationship between amyloid-controlled fungal programmed cell death and mammalian necroptosis.

scholarly journals Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 2836 ◽  
Author(s):  
Grace Mallett ◽  
Arian Laurence ◽  
Shoba Amarnath
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Surface Receptor ◽  
Programmed Cell Death 1 ◽  
Surface Receptor ◽  
A Cell ◽  
And Function

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.

Cell death in normal and rough eye mutants of Drosophila

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 825-839 ◽  
Author(s):  
T. Wolff ◽  
D.F. Ready
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Compound Eye ◽  
Cell Lineage ◽  
Cell Fates ◽  
Cone Cells ◽  
A Cell ◽  
Retinal Epithelium ◽  
Fly Eye ◽  
Dying Cells

The regular, reiterated cellular pattern of the Drosophila compound eye makes it a sensitive amplifier of defects in cell death. Quantitative and histological methods reveal a phase of cell death between 35 and 50 h of development which removes between 2 and 3 surplus cells per ommatidium. The timing of this epoch is consistent with cell death as the last fate to be specified in the progressive sequence of cell fates that build the ommatidium. An ultrastructural survey of cell death suggests dying cells in the fly eye have similarities as well as differences with standard descriptions of programmed cell death. A failure of cell death to remove surplus cells disorganizes the retinal lattice. A screen of rough eye mutants identifies two genes, roughest and echinus, required for the normal elimination of cells from the retinal epithelium. The use of an enhancer trap as a cell lineage marker shows that the cone cells, like other retinal cells, are not clonally related to each other or to their neighbors.

scholarly journals Stress Management in Cyst-Forming Free-Living Protists: Programmed Cell Death and/or Encystment

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Naveed Ahmed Khan ◽  
Junaid Iqbal ◽  
Ruqaiyyah Siddiqui
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Stress Management ◽  
Environmental Conditions ◽  
Free Living ◽  
Cyst Form ◽  
The Face ◽  
A Cell ◽  
Cellular Machinery ◽  
Harsh Conditions

In the face of harsh conditions and given a choice, a cell may (i) undergo programmed cell death, (ii) transform into a cancer cell, or (iii) enclose itself into a cyst form. In metazoans, the available evidence suggests that cellular machinery exists only to execute or avoid programmed cell death, while the ability to form a cyst was either lost or never developed. For cyst-forming free-living protists, here we pose the question whether the ability to encyst was gained at the expense of the programmed cell death or both functions coexist to counter unfavorable environmental conditions with mutually exclusive phenotypes.

scholarly journals Temperature dependence of intracellular Ca2+ homeostasis in rat meiotic and postmeiotic spermatogenic cells

Reproduction ◽  
2001 ◽  
pp. 545-551 ◽  
Author(s):  
E Herrera ◽  
K Salas ◽  
N Lagos ◽  
DJ Benos ◽  
JG Reyes
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
High Temperatures ◽  
Cell Parameter ◽  
Activation Energies ◽  
Extreme Temperatures ◽  
Spermatogenic Cells ◽  
A Cell ◽  
Pachytene Spermatocytes ◽  
Calculated Activation

The hypothesis that intracellular [Ca2+] is a cell parameter responsive to extreme temperatures in rat meiotic and postmeiotic spermatogenic cells was tested using intracellular fluorescent probes for Ca2+ and pH. In agreement with this hypothesis, extreme temperatures induced a rapid increase of cytosolic [Ca2+] in rat pachytene spermatocytes and round spermatids. Oscillatory changes in temperature can induce oscillations in cytosolic [Ca2+] in these cells. Intracellular [Ca2+] homeostasis in round spermatids was more sensitive to high temperatures compared with pachytene spermatocytes. The calculated activation energies for SERCA ATPase-mediated fluxes in pachytene spermatocytes and round spermatids were 62 and 75 kJ mol(-1), respectively. The activation energies for leak fluxes from intracellular Ca2+ stores were 55 and 68 kJ mol(-1) for pachytene spermatocytes and round spermatids, respectively. Together with changes in cytosolic [Ca2+], round spermatids undergo a decrease in pH(i) at high temperatures. This temperature-induced decrease in pH(i) appears to be partially responsible for the increase in cytosolic [Ca2+] of round spermatids induced by high temperatures. This characteristic of rat meiotic and postmeiotic spermatogenic cells to undergo an increment in cytosolic Ca2+ at temperatures > 33 degrees C can be related to the induction of programmed cell death by high temperatures in these cells.

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