scholarly journals Synergid Cell Death in Arabidopsis Is Triggered following Direct Interaction with the Pollen Tube

2007 ◽  
Vol 144 (4) ◽  
pp. 1753-1762 ◽  
Author(s):  
Linda Sandaklie-Nikolova ◽  
Ravishankar Palanivelu ◽  
Edward J. King ◽  
Gregory P. Copenhaver ◽  
Gary N. Drews
Keyword(s):  
Cell Death ◽  
Pollen Tube ◽  
Direct Interaction ◽  
Synergid Cell

scholarly journals Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2884 ◽  
Author(s):  
Eun-Jung In ◽  
Yuno Lee ◽  
Sushruta Koppula ◽  
Tae-Yeon Kim ◽  
Jun-Hyuk Han ◽  
...  
Keyword(s):  
Cell Death ◽  
Md Simulation ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Tnf Α

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.

scholarly journals Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK

2021 ◽  
Author(s):  
Andris Elksnis ◽  
Tomas A Schiffer ◽  
Fredrik Palm ◽  
Yun Wang ◽  
Jing Cen ◽  
...  
Keyword(s):  
Cell Death ◽  
Tyrosine Kinase ◽  
Beta Cell ◽  
Mitochondrial Respiration ◽  
Kinase Inhibitor ◽  
Direct Interaction ◽  
Ampk Activation ◽  
Beta Cell Death ◽  
Compound C

The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies, but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of NOD mice with imatinib resulted in increased beta-cell AMPK phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against IAPP-aggregation, TXNIP upregulation and beta-cell death. AICAR mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids/malate, possibly via a direct interaction with the beta-oxidation enzyme ECHS1. In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and ACC phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP downregulation, which in turn protects against beta-cell death.

scholarly journals Diablo Promotes Apoptosis by Removing Miha/Xiap from Processed Caspase 9

2001 ◽  
Vol 152 (3) ◽  
pp. 483-490 ◽  
Author(s):  
Paul G. Ekert ◽  
John Silke ◽  
Christine J. Hawkins ◽  
Anne M. Verhagen ◽  
David L. Vaux
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Caspase 3 ◽  
Direct Interaction ◽  
Inhibitor Of Apoptosis ◽  
Caspase 9 ◽  
Inhibitor Of Apoptosis Protein ◽  
Grim Reaper ◽  
Apoptosis Protein ◽  
Mammalian Protein

MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here, we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis.

scholarly journals The SEEL Motif and Members of the MYB-related REVEILLE Transcription Factor Family are Important for the Expression of LORELEI in the Synergid Cells of the Arabidopsis Female Gametophyte

2021 ◽  
Author(s):  
Jennifer A. Noble ◽  
Alex Seddon ◽  
Sahra Uygun ◽  
Steven E. Smith ◽  
Shin-Han Shiu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pollen Tube ◽  
Female Gametophyte ◽  
Regulatory Networks ◽  
Clock Genes ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Loss Of Function ◽  
Seed Formation ◽  
Synergid Cell

Synergid cells in the micropylar end of the female gametophyte are required for critical cell-cell signaling interactions between the pollen tube and the ovule that precede double fertilization and seed formation in flowering plants. LORELEI (LRE) encodes a GPI-anchored protein that is expressed primarily in the synergid cells, and together with FERONIA, a receptor-like kinase, it controls pollen tube reception by the receptive synergid cell. Still, how LRE expression is controlled in synergid cells remains poorly characterized. We identified candidate cis-regulatory elements enriched in LRE and other synergid cell-expressed genes. One of the candidate motifs (TAATATCT) in the LRE promoter was an uncharacterized variant of the Evening Element motif that we named as the Short Evening Element-like (SEEL) motif. Deletion or point mutations in the SEEL motif of the LRE promoter resulted in decreased reporter expression in synergid cells, demonstrating that the SEEL motif is important for expression of LRE in synergid cells. Additionally, we found that LRE expression is decreased in the loss of function mutants of REVEILLE (RVE) transcription factors, which are clock genes known to bind the SEEL and other closely related motifs. We propose that RVE transcription factors regulate LRE expression in synergid cells by binding to the SEEL motif in the LRE promoter. Identification of a cis-regulatory element and transcription factors involved in the expression of LRE will serve as a foundation to characterize the gene regulatory networks in synergid cells and investigate the potential connection between circadian rhythm and fertilization.

scholarly journals Cardiomyocyte differentiation from iPS cells is delayed following knockout of Bcl-2

2022 ◽  
Author(s):  
Tim Vervliet ◽  
Robin Duelen ◽  
lLewelyn H Roderick ◽  
Maurilio Sampaolesi
Keyword(s):  
Cell Death ◽  
Pluripotent Stem Cells ◽  
Direct Interaction ◽  
B Cell Lymphoma ◽  
Ips Cells ◽  
Cardiomyocyte Differentiation ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Induced Pluripotent

Anti-apoptotic B-cell lymphoma 2 (Bcl-2) regulates a wide array of cellular functions involved in cell death, cell survival decisions and autophagy. Bcl-2 acts by both direct interaction with different components of the pathways involved and by intervening in intracellular Ca2+ signalling. The function of Bcl-2 is in turn regulated by post-translational modifications including phosphorylation at different sites by various kinases. Besides functions in cell death and apoptosis, Bcl-2 regulates cell differentiation processes, including of cardiomyocytes, although the signalling pathways involved are not fully elucidated. To further address the role of Bcl-2 during cardiomyocyte differentiation, we investigated the effect of its genetic knockout by CRISPR/Cas9 on the differentiation and functioning of human induced pluripotent stem cells to cardiomyocytes. Our results indicate that differentiation of iPS cells to cardiomyocytes is delayed by Bcl-2 KO, resulting in reduced size of spontaneously beating cells and reduced expression of cardiomyocyte Ca2+ toolkit and functionality. These data thus indicate that Bcl-2 an essential protein for cardiomyocyte generation.

scholarly journals The different mechanisms of gametophytic self–incompatibility

2003 ◽  
Vol 358 (1434) ◽  
pp. 1025-1032 ◽  
Author(s):  
Vernonica E. Franklin-Tong ◽  
F. C. H. Franklin
Keyword(s):  
Complex System ◽  
Signal Transduction ◽  
Cell Death ◽  
Pollen Tube ◽  
The Other ◽  
Self Incompatibility ◽  
Signal Transduction Cascade ◽  
Two Systems

Self–incompatibility (SI) involves the recognition and rejection of self or genetically identical pollen. Gametophytic SI is probably the most widespread of the SI systems and, so far, two completely different SI mechanisms, which appear to have evolved separately, have been identified. One mechanism is the RNase system, which is found in the Solanaceae, Rosaceae and Scrophulariaceae. The other is a complex system, so far found only in the Papaveraceae, which involves the triggering of signal transduction cascade(s) that result in rapid pollen tube inhibition and cell death. Here, we present an overview of what is currently known about the mechanisms involved in controlling pollen tube inhibition in these two systems.

scholarly journals In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death

2004 ◽  
Vol 377 (2) ◽  
pp. 347-355 ◽  
Author(s):  
Heftsi AZOULAY-ZOHAR ◽  
Adrian ISRAELSON ◽  
Salah ABU-HAMAD ◽  
Varda SHOSHAN-BARMATZ
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Direct Interaction ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Metabolic Intermediate ◽  
Voltage Dependent

In tumour cells, elevated levels of mitochondria-bound isoforms of hexokinase (HK-I and HK-II) result in the evasion of apoptosis, thereby allowing the cells to continue proliferating. The molecular mechanisms by which bound HK promotes cell survival are not yet fully understood. Our studies relying on the purified mitochondrial outer membrane protein VDAC (voltage-dependent anion channel), isolated mitochondria or cells in culture suggested that the anti-apoptotic activity of HK-I occurs via modulation of the mitochondrial phase of apoptosis. In the present paper, a direct interaction of HK-I with bilayer-reconstituted purified VDAC, inducing channel closure, is demonstrated for the first time. Moreover, HK-I prevented the Ca2+-dependent opening of the mitochondrial PTP (permeability transition pore) and release of the pro-apoptotic protein cytochrome c. The effects of HK-I on VDAC activity and PTP opening were prevented by the HK reaction product glucose 6-phosphate, a metabolic intermediate in most biosynthetic pathways. Furthermore, glucose 6-phosphate re-opened both the VDAC and the PTP closed by HK-I. The HK-I-mediated effects on VDAC and PTP were not observed using either yeast HK or HK-I lacking the N-terminal hydrophobic peptide responsible for binding to mitochondria, or in the presence of an antibody specific for the N-terminus of HK-I. Finally, HK-I overexpression in leukaemia-derived U-937 or vascular smooth muscle cells protected against staurosporine-induced apoptosis, with a decrease of up to 70% in cell death. These results offer insight into the mechanisms by which bound HK promotes tumour cell survival, and suggests that its overexpression not only ensures supplies of energy and phosphometabolites, but also reflects an anti-apoptotic defence mechanism.

scholarly journals Biphasic Functional Interaction between the Adenovirus E4orf4 Protein and DNA-PK

2019 ◽  
Vol 93 (10) ◽  
Author(s):  
Keren Nebenzahl-Sharon ◽  
Hassan Shalata ◽  
Rakefet Sharf ◽  
Jana Amer ◽  
Hanan Khoury-Haddad ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Virus Replication ◽  
Dna Damage Response ◽  
Late Phase ◽  
Direct Interaction ◽  
Dependent Manner ◽  
Functional Interaction ◽  
Cancer Cell Death ◽  
Damage Response

ABSTRACTThe adenovirus (Ad) E4orf4 protein contributes to virus-induced inhibition of the DNA damage response (DDR) by reducing ATM and ATR signaling. Consequently, E4orf4 inhibits DNA repair and sensitizes transformed cells to killing by DNA-damaging drugs. Inhibition of ATM and ATR signaling contributes to the efficiency of virus replication and may provide one explanation for the cancer selectivity of cell death induced by the expression of E4orf4 alone. In this report, we investigate a direct interaction of E4orf4 with the DDR. We show that E4orf4 physically associates with the DNA-dependent protein kinase (DNA-PK), and we demonstrate a biphasic functional interaction between these proteins, wherein DNA-PK is required for ATM and ATR inhibition by E4orf4 earlier during infection but is inhibited by E4orf4 as infection progresses. This biphasic process is accompanied by initial augmentation and a later inhibition of DNA-PK autophosphorylation as well as by colocalization of DNA-PK with early Ad replication centers and distancing of DNA-PK from late replication centers. Moreover, inhibition of DNA-PK improves Ad replication more effectively when a DNA-PK inhibitor is added later rather than earlier during infection. When expressed alone, E4orf4 is recruited to DNA damage sites in a DNA-PK-dependent manner. DNA-PK inhibition reduces the ability of E4orf4 to induce cancer cell death, likely because E4orf4 is prevented from arriving at the damage sites and from inhibiting the DDR. Our results support an important role for the E4orf4–DNA-PK interaction in Ad replication and in facilitation of E4orf4-induced cancer-selective cell death.IMPORTANCESeveral DNA viruses evolved mechanisms to inhibit the cellular DNA damage response (DDR), which acts as an antiviral defense system. We present a novel mechanism by which the adenovirus (Ad) E4orf4 protein inhibits the DDR. E4orf4 interacts with the DNA damage sensor DNA-PK in a biphasic manner. Early during infection, E4orf4 requires DNA-PK activity to inhibit various branches of the DDR, whereas it later inhibits DNA-PK itself. Furthermore, although both E4orf4 and DNA-PK are recruited to virus replication centers (RCs), DNA-PK is later distanced from late-phase RCs. Delayed DNA-PK inhibition greatly contributes to Ad replication efficiency. When E4orf4 is expressed alone, it is recruited to DNA damage sites. Inhibition of DNA-PK prevents both recruitment and the previously reported ability of E4orf4 to kill cancer cells. Our results support an important role for the E4orf4–DNA-PK interaction in Ad replication and in facilitation of E4orf4-induced cancer-selective cell death.

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