Cell Suicide and Cell Death

1971 ◽  
pp. 163-173 ◽  
Author(s):  
E. Farber ◽  
R. S. Verbin ◽  
M. Lieberman
Keyword(s):  
Cell Death ◽  
Cell Suicide

scholarly journals Bacterial Ribonuclease MazF-Mediated Apoptosis as Potential Cancer Therapy

2021 ◽  
Author(s):  
Maryam Saffarian Abbas Zadeh ◽  
Rebecca Anne MacPherson ◽  
Guohui Huang ◽  
Hui Ding ◽  
Rhonda Reigers Powell ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Cell Lines ◽  
Mrna Translation ◽  
Protein Translation ◽  
Programmed Death ◽  
Inhibition Of Protein Synthesis ◽  
Cancer Agent ◽  
Cell Suicide ◽  
The Impact

Abstract Programmed cell death is a dynamic and critical mechanism of cell suicide in eukaryotes and prokaryotes. MazF is a ribonuclease protein involved in bacterial intracellular programmed death. This protein cleaves mRNAs at ACA sequences, leading to inhibition of protein synthesis and triggering cell death. Given that cancer is heterogenic and has varied susceptibility to treatment, we examined the impact of MazF proteins on the growth and viability of three cancer cell lines: MCF7, HT29, and AGS. These cell lines were transfected with ACA-less mazF mRNAs and evaluated for MazF-mediated cell death. The data illustrated that efficient MazF translation leads to a significant reduction in cell viability and is modulated by structural elements of ACA-less mazF mRNAs. In the presence of MazF, the levels of activated caspase-3 and -7 were significantly elevated in transfected cells, confirming the occurrence of apoptosis. We also quantified mRNA translation on a single-cell basis in MCF7 and AGS cell lines to examine MazF-mediated inhibition of protein synthesis. MazF expression significant decreases the levels of protein translation in the examined cell lines. This is the first report of MazF as a potential anti-cancer agent via induction of apoptosis in MCF7, AGS, and HT-29 cell lines.

scholarly journals Genome digestion is a dispensable consequence of physiological cell death mediated by cytotoxic T lymphocytes.

1992 ◽  
Vol 12 (7) ◽  
pp. 3060-3069 ◽  
Author(s):  
D S Ucker ◽  
P S Obermiller ◽  
W Eckhart ◽  
J R Apgar ◽  
N A Berger ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytotoxic T Lymphocyte ◽  
Death Process ◽  
Cell Nuclei ◽  
Calcium Dependent ◽  
Nuclear Envelope Breakdown ◽  
Murine Fibroblast ◽  
Cell Death Process ◽  
Cell Suicide ◽  
Physiological Cell Death

We examined virally transformed murine fibroblast clones as targets for cytotoxic T lymphocyte (CTL)-triggered lysis and genome digestion. Strikingly, while all clones were essentially equivalent in the ability to be lysed, one clone, SV3T3-B2.1, failed to exhibit genome digestion associated with CTL attack. Other aspects of the physiological cell death process, including loss of adhesion and nuclear envelope breakdown (lamin phosphorylation and solubilization), were not altered in this clone. The absence of genome digestion associated with CTL-induced cell death correlated with the absence of endodeoxyribonuclease activity in the nuclei of that clone. Characterization of the activity affected identifies a calcium-dependent, DNase I-like endonuclease of approximately 40 kDa, normally present constitutively in all cell nuclei, as the enzyme responsible for genome digestion associated with CTL-mediated cell death. These observations indicate that neither genome digestion per se nor its consequences [such as activation of poly(ADP-ribose) polymerase] are essential for cell death resulting from the triggering of this cell suicide process.

Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms

1994 ◽  
Vol 14 (1) ◽  
pp. 427-436
Author(s):  
D S Ucker ◽  
J D Wilson ◽  
L D Hebshi
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Active Cell ◽  
Death Process ◽  
Target Cells ◽  
Antigenic Stimulus ◽  
Cell Suicide

The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes to the target the single role of providing an antigenic stimulus to the CTL; this signal results in the vectoral degranulation and secretion of pore-forming elements onto the target. On the other hand, by a number of criteria, target cell death triggered by CTL appears fundamentally different from death resulting from membrane damage and osmotic lysis. CTL-triggered target cell death involves primary internal lesions of the target cell that reflect a physiological cell death process. Orderly nuclear disintegration, including lamin phosphorylation and solubilization, chromatin condensation, and genome digestion, are among the earliest events, preceding the loss of plasma membrane integrity. We have tested directly the involvement of the target cell in its own death by examining whether we could isolate mutants of target cells that have retained the ability to be recognized by and provide an antigenic stimulus to CTL while having lost the capacity to respond by dying. Here, we describe one such mutant, BW87. We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered target cell death under a variety of conditions. The identification of a mutable target cell element essential for the cell death response to CTL provides genetic evidence that target cell death reflects an active cell suicide process similar to other physiological cell deaths.

Genome digestion is a dispensable consequence of physiological cell death mediated by cytotoxic T lymphocytes

1992 ◽  
Vol 12 (7) ◽  
pp. 3060-3069
Author(s):  
D S Ucker ◽  
P S Obermiller ◽  
W Eckhart ◽  
J R Apgar ◽  
N A Berger ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytotoxic T Lymphocyte ◽  
Death Process ◽  
Cell Nuclei ◽  
Calcium Dependent ◽  
Nuclear Envelope Breakdown ◽  
Murine Fibroblast ◽  
Cell Death Process ◽  
Cell Suicide ◽  
Physiological Cell Death

We examined virally transformed murine fibroblast clones as targets for cytotoxic T lymphocyte (CTL)-triggered lysis and genome digestion. Strikingly, while all clones were essentially equivalent in the ability to be lysed, one clone, SV3T3-B2.1, failed to exhibit genome digestion associated with CTL attack. Other aspects of the physiological cell death process, including loss of adhesion and nuclear envelope breakdown (lamin phosphorylation and solubilization), were not altered in this clone. The absence of genome digestion associated with CTL-induced cell death correlated with the absence of endodeoxyribonuclease activity in the nuclei of that clone. Characterization of the activity affected identifies a calcium-dependent, DNase I-like endonuclease of approximately 40 kDa, normally present constitutively in all cell nuclei, as the enzyme responsible for genome digestion associated with CTL-mediated cell death. These observations indicate that neither genome digestion per se nor its consequences [such as activation of poly(ADP-ribose) polymerase] are essential for cell death resulting from the triggering of this cell suicide process.

scholarly journals Autophagy and cell death: The jury's still out

2012 ◽  
Vol 34 (2) ◽  
pp. 14-19
Author(s):  
Jon D. Lane ◽  
Virginie M.S. Betin ◽  
Lilith Mannack ◽  
Tom D.B. MacVicar
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mammalian Cells ◽  
Autophagic Cell Death ◽  
Circumstantial Evidence ◽  
Innocent Bystander ◽  
Catastrophic Loss ◽  
A Cell ◽  
Cell Suicide ◽  
Timely Death

Since the publication of seminal work in the early 1970s by John Kerr and Andrew Wyllie1, we have been aware that mammalian cells have the genetically encoded capability to give up the ghost and trigger a highly conserved cell-suicide pathway called apoptosis. Not content with this important knowledge, many researchers have spent the intervening years attempting to identify and characterize other ‘programmed cell death’ (PCD) mechanisms that might also have important roles in development and disease. One of these was ‘autophagy’, a process by which cells became vacuolated and progressively devoid of cytoplasm. Over the years, ‘autophagic cell death’ has been linked with the timely death of cells in development, as well as the catastrophic loss of cells in several important human diseases. But is autophagy truly a cell death mechanism in its own right? Perhaps it is just an innocent bystander, unfairly accused on the basis of flimsy circumstantial evidence? The jury may finally be poised to return a decisive verdict….

scholarly journals Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells

Oncogene ◽  
1999 ◽  
Vol 18 (13) ◽  
pp. 2281-2290 ◽  
Author(s):  
Shunji Chi ◽  
Chifumi Kitanaka ◽  
Kohji Noguchi ◽  
Toshihiro Mochizuki ◽  
Yohji Nagashima ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Oncogenic Ras ◽  
Cell Death Program ◽  
Cell Suicide

scholarly journals Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms.

1994 ◽  
Vol 14 (1) ◽  
pp. 427-436 ◽  
Author(s):  
D S Ucker ◽  
J D Wilson ◽  
L D Hebshi
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Active Cell ◽  
Death Process ◽  
Target Cells ◽  
Antigenic Stimulus ◽  
Cell Suicide

The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes to the target the single role of providing an antigenic stimulus to the CTL; this signal results in the vectoral degranulation and secretion of pore-forming elements onto the target. On the other hand, by a number of criteria, target cell death triggered by CTL appears fundamentally different from death resulting from membrane damage and osmotic lysis. CTL-triggered target cell death involves primary internal lesions of the target cell that reflect a physiological cell death process. Orderly nuclear disintegration, including lamin phosphorylation and solubilization, chromatin condensation, and genome digestion, are among the earliest events, preceding the loss of plasma membrane integrity. We have tested directly the involvement of the target cell in its own death by examining whether we could isolate mutants of target cells that have retained the ability to be recognized by and provide an antigenic stimulus to CTL while having lost the capacity to respond by dying. Here, we describe one such mutant, BW87. We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered target cell death under a variety of conditions. The identification of a mutable target cell element essential for the cell death response to CTL provides genetic evidence that target cell death reflects an active cell suicide process similar to other physiological cell deaths.

scholarly journals Ceramide-induced cell death/survival in murine osteoblasts

2010 ◽  
Vol 206 (2) ◽  
pp. 225-233 ◽  
Author(s):  
P A Hill ◽  
A Tumber
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cell Types ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitors ◽  
Diphenyl Tetrazolium Bromide ◽  
General Protein ◽  
Pkc Ζ ◽  
Cell Suicide

Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. We determined whether ceramide treatment contributes to reduced cell viability and increased PCD in primary osteoblasts and the signalling pathways that are involved. Cell viability was determined by the 3-(4,5-dimethyl-thiozol-2-yl)-2,5-diphenyl tetrazolium bromide assay. We found that C2-ceramide (≤10−7 M) promoted osteoblast viability, whilst concentrations ≥2×10−6 M significantly reduced osteoblast viability in a dose- and time-dependent manner. The effect of ceramide on cell viability was specific since C2-dihydroceramide had no effect. Increasing intracellular ceramide levels with either sphingomyelinase (SMase) or an inhibitor of ceramide metabolism also increased osteoblast apoptosis. Ceramide-induced PCD in osteoblasts was determined by nuclear appearance and DNA fragmentation. PCD was induced by both C2-ceramide and SMase. The ability of ceramide (5×10−8 M) to promote osteoblast survival was prevented by a general protein kinase C (PKC) inhibitor and by a PKC ζ inhibitor, whilst osteoblast survival was enhanced in the presence of a protein phosphatase 1 (PP1) inhibitor. Phosphatidylinositol-3 kinase (PI3K) inhibitors had no effect on osteoblast survival. The ability of ceramide (5×10−5 M) to induce apoptosis was prevented by the inhibitors of PP1 and PKC δ, whilst the general PKC and PI3K inhibitors had no effect on it. Our findings suggest that ceramide signals osteoblast survival and apoptosis through different intracellular pathways, and that alteration in the intracellular levels of ceramide may play an important role in bone remodelling.

scholarly journals Why yeast cells can undergo apoptosis: death in times of peace, love, and war

2006 ◽  
Vol 175 (4) ◽  
pp. 521-525 ◽  
Author(s):  
Sabrina Büttner ◽  
Tobias Eisenberg ◽  
Eva Herker ◽  
Didac Carmona-Gutierrez ◽  
Guido Kroemer ◽  
...  
Keyword(s):  
Cell Death ◽  
Single Cells ◽  
Yeast Cells ◽  
Unicellular Organism ◽  
Killer Toxins ◽  
Cell Biol ◽  
Cell Death Program ◽  
A Cell ◽  
Multicellular Organisms ◽  
Cell Suicide

The purpose of apoptosis in multicellular organisms is obvious: single cells die for the benefit of the whole organism (for example, during tissue development or embryogenesis). Although apoptosis has also been shown in various microorganisms, the reason for this cell death program has remained unexplained. Recently published studies have now described yeast apoptosis during aging, mating, or exposure to killer toxins (Fabrizio, P., L. Battistella, R. Vardavas, C. Gattazzo, L.L. Liou, A. Diaspro, J.W. Dossen, E.B. Gralla, and V.D. Longo. 2004. J. Cell Biol. 166:1055–1067; Herker, E., H. Jungwirth, K.A. Lehmann, C. Maldener, K.U. Frohlich, S. Wissing, S. Buttner, M. Fehr, S. Sigrist, and F. Madeo. 2004. J. Cell Biol. 164:501–507, underscoring the evolutionary benefit of a cell suicide program in yeast and, thus, giving a unicellular organism causes to die for.

scholarly journals Sindbis Virus Induces Apoptosis through a Caspase-Dependent, CrmA-Sensitive Pathway

1998 ◽  
Vol 72 (1) ◽  
pp. 452-459 ◽  
Author(s):  
Victor E. Nava ◽  
Antony Rosen ◽  
Michael A. Veliuona ◽  
Rollie J. Clem ◽  
Beth Levine ◽  
...  
Keyword(s):  
Cell Death ◽  
Sindbis Virus ◽  
Cultured Cells ◽  
Cowpox Virus ◽  
Necrosis Factor Alpha ◽  
Viral Proteases ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Cell Suicide

ABSTRACT Sindbis virus infection of cultured cells and of neurons in mouse brains leads to programmed cell death exhibiting the classical characteristics of apoptosis. Although the mechanism by which Sindbis virus activates the cell suicide program is not known, we demonstrate here that Sindbis virus activates caspases, a family of death-inducing proteases, resulting in cleavage of several cellular substrates. To study the role of caspases in virus-induced apoptosis, we determined the effects of specific caspase inhibitors on Sindbis virus-induced cell death. CrmA (a serpin from cowpox virus) and zVAD-FMK (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) inhibited Sindbis virus-induced cell death, suggesting that cellular caspases facilitate apoptosis induced by Sindbis virus. Furthermore, CrmA significantly increased the rate of survival of infected mice. These inhibitors appear to protect cells by inhibiting the cellular death pathway rather than impairing virus replication or by inhibiting the nsP2 and capsid viral proteases. The specificity of CrmA indicates that the Sindbis virus-induced death pathway is similar to that induced by Fas or tumor necrosis factor alpha rather than being like the death pathway induced by DNA damage. Taken together, these data suggest a central role for caspases in Sindbis virus-induced apoptosis.

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