scholarly journals Meiotic viral attenuation through an ancestral apoptotic pathway

2019 ◽  
Author(s):  
Jie Gao ◽  
Sabrina Chau ◽  
Fuad Chowdhury ◽  
Tina Zhou ◽  
Saif Hossain ◽  
...  
Keyword(s):  
Budding Yeast ◽  
Apoptotic Pathway ◽  
Endonuclease G ◽  
Dying Cells ◽  
Viral Attenuation ◽  
Dsrna Mycovirus ◽  
Programmed Release

AbstractThe programmed release of apoptogenic proteins from mitochondria is a core event of apoptosis, though ancestral roles of this phenomenon are not known. In mammals, one such apoptogenic protein is Endonuclease G (EndoG), a conserved nuclease that fragments the DNA of dying cells. In this work, we show that budding yeast executes meiotically programmed mitochondrial release of an EndoG homologue, Nuc1, during sporulation. In contrast to EndoG’s ostensible pro-death function during apoptosis, Nuc1 mitochondrial release attenuates the cytosolic dsRNA mycovirus, Killer, protecting spores from a lethal accumulation of its encoded toxin. Our identification of cell-protective viral attenuation as a target of this rudimentary apoptotic pathway illuminates a primordial role for mitochondrial release of EndoG.One Sentence SummaryYeast sporulation induces release of mitochondrial endonuclease G to accomplish viral attenuation.

scholarly journals Meiotic viral attenuation through an ancestral apoptotic pathway

2019 ◽  
Vol 116 (33) ◽  
pp. 16454-16462 ◽  
Author(s):  
Jie Gao ◽  
Sabrina Chau ◽  
Fuad Chowdhury ◽  
Tina Zhou ◽  
Saif Hossain ◽  
...  
Keyword(s):  
Budding Yeast ◽  
Apoptotic Pathway ◽  
Double Stranded Rna ◽  
Endonuclease G ◽  
Dying Cells ◽  
Viral Attenuation ◽  
Programmed Release

The programmed release of apoptogenic proteins from mitochondria is a core event of apoptosis, although ancestral roles of this phenomenon are not known. In mammals, one such apoptogenic protein is Endonuclease G (EndoG), a conserved mitochondrial nuclease that fragments the DNA of dying cells. In this work, we show that budding yeast executes meiotically programmed mitochondrial release of an EndoG homolog, Nuc1, during sporulation. In contrast to EndoG’s ostensible pro-death function during apoptosis, Nuc1 mitochondrial release is pro-survival, attenuating the cytosolic L-A and Killer double-stranded RNA mycoviruses and protecting meiotic progeny from the catastrophic consequences of their derepression. The protective viral attenuation role of this pathway illuminates a primordial role for mitochondrial release of EndoG, and perhaps of apoptosis itself.

scholarly journals Cerebral Cortex Apoptosis in Early Aged Hypertension: Effects of Epigallocatechin-3-Gallate

2021 ◽  
Vol 13 ◽  
Author(s):  
Min-Huang Hsieh ◽  
Zhen-Yang Cui ◽  
Ai-Lun Yang ◽  
Nguyen Thanh Nhu ◽  
Shih-Ying Ting ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Green Tea ◽  
Fas Ligand ◽  
Therapeutic Effects ◽  
Apoptotic Pathway ◽  
Egcg Treatment ◽  
Endonuclease G ◽  
Survival Pathway ◽  
Wistar Kyoto ◽  
Apoptotic Pathways

This study aimed to investigate cerebral cortex apoptosis on the early aged hypertension and the effects of green tea flavonoid epigallocatechin-3-gallate (EGCG). Twenty-four rats were divided into three groups: a control Wistar-Kyoto group (WKY, n = 8), a spontaneously early aged hypertensive group (SHR, n = 8), and an early aged hypertension with EGCG treatment group (SHR-EGCG, n = 8; daily oral EGCG 200 mg/kg—94%, 12 weeks). At 48 weeks old, blood pressures (BPs) were evaluated and cerebral cortexes were isolated for TUNEL assay and Western blotting. Systolic, diastolic, and mean blood pressure levels in the SHR-EGCG were reduced compared to the SHR. The percentage of neural cell deaths, the levels of cytosolic Endonuclease G, cytosolic AIF (Caspase-independent apoptotic pathway), Fas, Fas Ligand, FADD, Caspase-8 (Fas-mediated apoptotic pathway), t-Bid, Bax/Bcl-2, Bak/Bcl-xL, cytosolic Cytochrome C, Apaf-1, Caspase-9 (Mitochondrial-mediated apoptotic pathway), and Caspase-3 (Fas-mediated and Mitochondria-mediated apoptotic pathways) were increased in the SHR relative to WKY and reduced in SHR-EGCG relative to SHR. In contrast, the levels of Bcl-2, Bcl-xL, p-Bad, 14-3-3, Bcl-2/Bax, Bcl-xL/Bak, and p-Bad/Bad (Bcl-2 family-related pro-survival pathway), as well as Sirt1, p-PI3K/PI3K and p-AKT/AKT (Sirt1/PI3K/AKT-related pro-survival pathway), were reduced in SHR relative WKY and enhanced in SHR-EGCG relative to SHR. In conclusion, green tea flavonoid epigallocatechin-3-gallate (EGCG) might prevent neural apoptotic pathways and activate neural survival pathways, providing therapeutic effects on early aged hypertension-induced neural apoptosis.

The Role of PNAS-2 in Apoptotic Pathway.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4092-4092
Author(s):  
Hai-Rong Wang ◽  
Hua Zhong ◽  
Ji-Hua Zhong ◽  
Fei Xiao ◽  
Jian-Yi Zhu ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Death Receptor ◽  
Multivesicular Body ◽  
Intermembrane Space ◽  
Intrinsic Apoptotic Pathway ◽  
Lysosomal Degradation ◽  
Antibody Microarray ◽  
Apoptotic Pathway ◽  
Endonuclease G ◽  
No Activation

Abstract We recently demonstrated PNAS-2 serving as both an anti-apoptotic gene and an oncogene which is specifically up-regulated in acute leukemic patients (Hai-Rong WANG, et al. Oncology, Accepted). However, its role in apoptotic pathway remains elusive. Antibody microarray was applied to study the apoptosis-associated proteins’ changes to elucidate its role in apoptotic pathway. After PNAS-2 was inhibited by RNA interference, caspase3 was up-regulated confirming that PNAS-2 had an anti-apoptotic function. The activation of extrinsic, receptor-mediated apoptotic pathway was characterized by binding a death ligand to the corresponding death receptor. In this study, there were no changes in TNFα, CD95/Fas, TNFR, FADD, TRADD and caspase8 though Fas ligand decreased, while the apoptotic inhibitors such as DcR1 and FLIP were up-regulated, indicating there was no activation in the extrinsic apoptotic pathway. As to the apoptogenic proteins of classical intrinsic apoptotic pathway, there were no changes in Bax and caspase 9 though Bim was down-regulated, while the apoptotic inhibitors such as Bcl-2, Bcl-XL were up-regulated, indicating there was no activation in the intrinsic apoptotic pathway as well. Apart from the two classical apoptotic pathways (intrinsic and extrinsic), Granzyme B (GraB)-perforin apoptotic pathway is one well defined extrinsic accessory way of triggering apoptosis. In our data, GraB and Perforin were up-regulated, suggesting the GraB-Perforin apoptotic pathway was also activated. The apoptosis-induced factor (AIF) and Cathepsin D (CatD) were also up-regulated. AIF could induce apoptosis via a caspase-independent pathway, and Cat D could selectively escape AIF from mitochondria when translocated into the cytosol from lysosome, while other apoptogenic proteins resided in the intermembrane space of mitochondria such as cytochrome c and endonuclease G remained in the mitochondria (Nicolas Bidere, et al. JBC, 2003). Our data indicated that the AIF-induced-caspase-independent pathway was activated when PNAS-2 was inhibited. The changes in protein levels of CatD, AIF and GraB were confirmed by Western Blot. Mannose-6-Phosphate receptor (M6Pr) is the target receptor for GraB and CatD, mediating uptake of the proteases to form vesicles via endocytosis. This receptor also serves to transport newly synthesized GraB and CatD into the vesicles. The vesicles would form a structure named multivesicular body (MVB), which served to sort vesicles’ content destined for degradation or routing to the lysosome. CHMP5 (the alias of PNAS-2) located in MVB and lysosome, and the loss of CHMP5/PNAS-2 could inhibit lysosomal degradation (Jae-Hyuck Shim, et al. JCB, 2006). As GraB and CatD could trigger apoptosis when they were effluxed from the lysosome, we hypothesize that the overexpression of PNAS-2 in leukemic patients might execute its anti-apoptotic function by increasing the lysosomal degradation of apoptogenic factors in lysosome such as CatD and GraB. Figure Figure

scholarly journals DRONC Coordinates Cell Death and Compensatory Proliferation

2006 ◽  
Vol 26 (19) ◽  
pp. 7258-7268 ◽  
Author(s):  
Shu Kondo ◽  
Nanami Senoo-Matsuda ◽  
Yasushi Hiromi ◽  
Masayuki Miura
Keyword(s):  
Cell Death ◽  
Imaginal Discs ◽  
Γ Irradiation ◽  
Apoptotic Pathway ◽  
Effector Caspase ◽  
Effector Caspases ◽  
Extensive Cell Death ◽  
Compensatory Proliferation ◽  
Extensive Cell ◽  
Dying Cells

ABSTRACT Accidental cell death often leads to compensatory proliferation. In Drosophila imaginal discs, for example, γ-irradiation induces extensive cell death, which is rapidly compensated by elevated proliferation. Excessive compensatory proliferation can be artificially induced by “undead cells” that are kept alive by inhibition of effector caspases in the presence of apoptotic stimuli. This suggests that compensatory proliferation is induced by dying cells as part of the apoptosis program. Here, we provide genetic evidence that the Drosophila initiator caspase DRONC governs both apoptosis execution and subsequent compensatory proliferation. We examined mutants of five Drosophila caspases and identified the initiator caspase DRONC and the effector caspase DRICE as crucial executioners of apoptosis. Artificial compensatory proliferation induced by coexpression of Reaper and p35 was completely suppressed in dronc mutants. Moreover, compensatory proliferation after γ-irradiation was enhanced in drice mutants, in which DRONC is activated but the cells remain alive. These results show that the apoptotic pathway bifurcates at DRONC and that DRONC coordinates the execution of cell death and compensatory proliferation.

scholarly journals Endonuclease G Regulates Budding Yeast Life and Death

2007 ◽  
Vol 25 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Sabrina Büttner ◽  
Tobias Eisenberg ◽  
Didac Carmona-Gutierrez ◽  
Doris Ruli ◽  
Heide Knauer ◽  
...  
Keyword(s):  
Budding Yeast ◽  
Endonuclease G ◽  
Life And Death

Absence of temporal ordering of apoptotic features in heat-shock treated leukemia and lymphoma cell lines

1996 ◽  
Vol 54 ◽  
pp. 758-759
Author(s):  
D. W. Fairbain ◽  
M.D. Standing ◽  
K.L. O'Neill
Keyword(s):  
Heat Shock ◽  
Cell Lines ◽  
Chromatin Condensation ◽  
Membrane Integrity ◽  
Resistant Cell ◽  
Membrane Blebbing ◽  
Late Loss ◽  
Induced Apoptosis ◽  
Dying Cells ◽  
In Cells

Apoptosis is a genetically defined response to physiological stimuli that results in cellular suicide. Features common to apoptotic cells include chromatin condensation, oligonucleosomal DNA fragmentation, membrane blebbing, nuclear destruction, and late loss of ability to exclude vital dyes. These characteristics contrast markedly from pathological necrosis, in which membrane integrity loss is demonstrated early, and other features of apoptosis, which allow a non-inflammatory removal of dead and dying cells, are absent. Using heat shock-induced apoptosis as a model for examining stress response in cells, we undertook to categorize a variety of human leukemias and lymphomas with regard to their response to heat shock. We were also interested in determining whether a common temporal order was followed in cells dying by apoptosis. In addition, based on our previous results, we investigated whether increasing heat load resulted in increased apoptosis, with particular interest in relatively resistant cell lines, or whether the mode of death changed from apoptosis to necrosis.

Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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