death signals
Recently Published Documents


TOTAL DOCUMENTS

87
(FIVE YEARS 10)

H-INDEX

30
(FIVE YEARS 1)

Author(s):  
Ok-Hee Kim ◽  
Geun-Hyung Kang ◽  
June Hur ◽  
Jinwook Lee ◽  
YunJae Jung ◽  
...  

AbstractApoptotic cells are rapidly engulfed and removed by phagocytes after displaying cell surface eat-me signals. Among many phospholipids, only phosphatidylserine (PS) is known to act as an eat-me signal on apoptotic cells. Using unbiased proteomics, we identified externalized phosphatidylinositides (PIPs) as apoptotic eat-me signals recognized by CD14+ phagocytes. Exofacial PIPs on the surfaces of early and late-apoptotic cells were observed in patches and blebs using anti-PI(3,4,5)P3 antibody, AKT- and PLCδ PH-domains, and CD14 protein. Phagocytosis of apoptotic cells was blocked either by masking exofacial PIPs or by CD14 knockout in phagocytes. We further confirmed that exofacial PIP+ thymocytes increased dramatically after in vivo irradiation and that exofacial PIP+ cells represented more significant populations in tissues of Cd14−/− than WT mice, especially after induction of apoptosis. Our findings reveal exofacial PIPs to be previously unknown cell death signals recognized by CD14+ phagocytes.


Science ◽  
2021 ◽  
pp. eabg7917
Author(s):  
Pierre Jacob ◽  
Nak Hyun Kim ◽  
Feihua Wu ◽  
Farid El-Kasmi ◽  
Yuan Chi ◽  
...  

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. In Arabidopsis, a subfamily of “helper” NLRs are required by many “sensor” NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta and conferred cytoplasmic Ca2+ influx in plant and human cells. NRG1.1-dependent Ca2+ influx and cell death were sensitive to Ca2+ channel blockers and were suppressed by mutations impacting oligomerization or plasma membrane enrichment. Ca2+ influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another “helper” NLR, required conserved negatively charged N-terminal residues. Whole-cell voltage-clamp recordings demonstrate that Arabidopsis “helper” NLRs form Ca2+-permeable cation channels to directly regulate cytoplasmic Ca2+ levels and consequent cell death. Thus, “helper” NLRs transduce cell death signals directly.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 657
Author(s):  
Nan Wang ◽  
Chong Wang ◽  
Hongyang Zhao ◽  
Yichun He ◽  
Beiwu Lan ◽  
...  

The maintenance of cellular homeostasis involves the participation of multiple organelles. These organelles are associated in space and time, and either cooperate or antagonize each other with regards to cell function. Crosstalk between organelles has become a significant topic in research over recent decades. We believe that signal transduction between organelles, especially the endoplasmic reticulum (ER) and mitochondria, is a factor that can influence the cell fate. As the cellular center for protein folding and modification, the endoplasmic reticulum can influence a range of physiological processes by regulating the quantity and quality of proteins. Mitochondria, as the cellular “energy factory,” are also involved in cell death processes. Some researchers regard the ER as the sensor of cellular stress and the mitochondria as an important actuator of the stress response. The scientific community now believe that bidirectional communication between the ER and the mitochondria can influence cell death. Recent studies revealed that the death signals can shuttle between the two organelles. Mitochondria-associated membranes (MAMs) play a vital role in the complex crosstalk between the ER and mitochondria. MAMs are known to play an important role in lipid synthesis, the regulation of Ca2+ homeostasis, the coordination of ER-mitochondrial function, and the transduction of death signals between the ER and the mitochondria. Clarifying the structure and function of MAMs will provide new concepts for studying the pathological mechanisms associated with neurodegenerative diseases, aging, and cancers. Here, we review the recent studies of the structure and function of MAMs and its roles involved in cell death, especially in apoptosis.


2020 ◽  
Vol 191 ◽  
pp. 109839
Author(s):  
Eun-Jung Park ◽  
Soo-Nam Kim ◽  
Gwang-Hee Lee ◽  
Young-Min Jo ◽  
Cheolho Yoon ◽  
...  

Burns ◽  
2020 ◽  
Vol 46 (6) ◽  
pp. 1389-1397
Author(s):  
Jiajun Feng ◽  
Moogaambikai Thangaveloo ◽  
Yee Siang Ong ◽  
Si Jack Chong ◽  
Janna-Vale Joethy ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Livio Casarini ◽  
Clara Lazzaretti ◽  
Elia Paradiso ◽  
Silvia Limoncella ◽  
Laura Riccetti ◽  
...  

Abstract Mechanisms regulating the selection of antral ovarian follicles are poorly understood and supposed to rely on low estrogen levels, decline of follicle-stimulating hormone (FSH) levels and receptor (FSHR) expression. These concepts are challenged in vitro, where apoptosis of human granulosa cells (hGLC) and transfected cell lines is induced by high doses of FSH or FSHR overexpression, while estrogens induce anti-apoptotic signals via nuclears and a G protein-coupled estrogen receptor (GPER). Therefore, in vitro data suggest that antral follicle selection may be driven by underestimated, FSH/FSHR-dependent apoptotic signals due to transiently maximized FSHR expression and overload of cAMP signalling, prevailing on estrogen-dependent signals. Here we demonstrate how FSHR/GPER physical interaction rescue ovarian follicles from FSH-mediated death. 10 nM FSH induces high intracellular levels of cAMP, measured by bioluminescence resonance energy transfer (BRET), and apoptosis in cultured hGLC under conditions where GPER levels are depleted by siRNA. This result was confirmed in transfected HEK293 cells overexpressing FSHR. Using BRET, photo-activated localization microscopy (PALM) and bioinformatics prodiction, we also demonstrate FSHR/GPER heteromers at the cell surface. The role of FSHR/GPER heteromers may be relevant to inhibit FSH-induced death signals, since increasing GPER expression levels in HEK293 cells co-expressing FSHR results in displacement of the Gαs-protein to FSHR, blockade of FSH-induced cAMP production and inhibition of apoptosis. However, in HEK293 cells coexpressing GPER/FSHR, FSH-induced activation of the anti-apoptotic AKT-pathway via a Gβγ-dependent mechanism, as demonstrated by Western blotting in cells treated using the inhibitor gallein. Inhibition of both FSH-induced cAMP production and apoptosis was lost when FSHR is coexpressed together with a mutant GPER, unable to heteromerize with FSHR, as well as in KO HEK293 cells unable to produce a molecular complex associated with GPER inhibiting cAMP. GPER/FSHR coexpression is confirmed in secondary follicles from paraffin-embedded tissues of human ovary by immunohistochemistry, suggesting that FSHR-GPER heterodimers could be physiologically relevant in vivo for inhibiting cAMP-linked apoptosis. Most importantly, FSHR and GPER co-expression correlates in hGLC from FSH-normo-responder women undergoing assisted reproduction, while it is not in hGLC from FSH-poor-responders, where increasing FSHR mRNA levels do not correspond to increasing GPER mRNA levels. We demonstrate that death signals in atretic follicles are delivered through overexpressed FSHR and inhibited by FSHR/GPER heteromerization, activating anti-apoptotic pathways. This finding unveils a novel working model of the physiology of dominant follicle selection and the relationship between FSH and estrogens.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Yanina Tsenkina ◽  
Stephen A Tapanes ◽  
Madelen M Díaz ◽  
David J Titus ◽  
Shyam Gajavelli ◽  
...  

Abstract Clinical trials examining neuroprotective strategies after brain injury, including those targeting cell death mechanisms, have been underwhelming. This may be in part due to an incomplete understanding of the signalling mechanisms that induce cell death after traumatic brain injury. The recent identification of a new family of death receptors that initiate pro-cell death signals in the absence of their ligand, called dependence receptors, provides new insight into the factors that contribute to brain injury. Here, we show that blocking the dependence receptor signalling of EphB3 improves oligodendrocyte cell survival in a murine controlled cortical impact injury model, which leads to improved myelin sparing, axonal conductance and behavioural recovery. EphB3 also functions as a cysteine-aspartic protease substrate, where the recruitment of injury-dependent adaptor protein Dral/FHL-2 together with capsase-8 or -9 leads to EphB3 cleavage to initiate cell death signals in murine and human traumatic brain-injured patients, supporting a conserved mechanism of cell death. These pro-apoptotic responses can be blocked via exogenous ephrinB3 ligand administration leading to improved oligodendrocyte survival. In short, our findings identify a novel mechanism of oligodendrocyte cell death in the traumatically injured brain that may reflect an important neuroprotective strategy in patients.


2019 ◽  
Vol 317 (1) ◽  
pp. C111-C130 ◽  
Author(s):  
Darin Bloemberg ◽  
Joe Quadrilatero

Apoptosis and autophagy are processes resulting from the integration of cellular stress and death signals. Their individual importance is highlighted by the lethality of various mouse models missing apoptosis or autophagy-related genes. In addition to their independent roles, significant overlap exists with respect to the signals that stimulate these processes as well as their effector consequences. While these cellular systems exemplify the programming redundancies that underlie many fundamental biological mechanisms, their intertwined relationship means that dysfunction can promote pathology. Although both autophagic and apoptotic signaling are active in skeletal muscle during various diseases and atrophy, their specific roles here are somewhat unique. Given our growing understanding of how specific changes at the cellular level impact whole-organism physiology, there is an equally growing interest in pharmacological manipulation of apoptosis and/or autophagy for altering human physiology and health.


Sign in / Sign up

Export Citation Format

Share Document