Role of the cytoskeleton in Cd2+-induced death of mouse mesangial cellsThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 341-352 ◽  
Author(s):  
Ying Liu ◽  
Douglas M. Templeton
Keyword(s):  
Cell Death ◽  
Mesangial Cells ◽  
Apoptotic Cell ◽  
Cytochalasin D ◽  
Ros Production ◽  
Filamentous Actin ◽  
P38 Kinase ◽  
Apoptotic Death ◽  
Dependent Cell

Cadmium induces apoptotic cell death in mouse mesangial cells that is in part dependent on reactive oxygen species (ROS). Cadmium also activates multiple kinases in these cells, including the Ca2+/calmodulin-dependent protein kinase II (CaMK-II) and p38 kinase, and also leads to disruption of the filamentous actin cytoskeleton. We investigated the role of the cytoskeleton in Cd2+-induced cell death. Cell viability was decreased by Cd2+and two types of apoptotic death, defined by flow cytometry, were increased. Disruption of actin filaments with cytochalasin D was partially protective, whereas stabilization of the cytoskeleton with jasplakinolide was without effect, indicating that cytoskeletal disruption contributes to, but is not necessary for, induction of apoptosis. Inhibition of CaMK-II and p38 kinase, mitochondrial stabilization with cyclosporine A, and the antioxidant N-acetyl cysteine all protected against apoptosis and prevented disruption of the cytoskeleton. Cytochalasin D decreased Cd2+-dependent ROS production, reduced the decline in mitochondrial membrane potential, and decreased phosphorylation of p38 kinase. We conclude that Cd2+-dependent actin disruption is a downstream event facilitating apoptotic death. Cadmium-dependent cell death involves actin-dependent mitochondrial changes, ROS production, and p38 activation.

scholarly journals Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 376
Author(s):  
Chantal B. Lucini ◽  
Ralf J. Braun
Keyword(s):  
Cell Death ◽  
Oxygen Species ◽  
In Vivo Models ◽  
Dependent Cell ◽  
Cell Death Mechanisms ◽  
Sting Pathway ◽  
Mitochondrial Membrane Permeabilization

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.

Improved cellular automata model shows that indirect apoptotic cell death due to vascular damage enhances the local control of tumors by single fraction high-dose irradiation

2021 ◽  
Author(s):  
Daisuke Kawahara ◽  
Yasushi Nagata ◽  
Yoichi Watanabe
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Radiation Damage ◽  
Apoptotic Cell ◽  
Vascular Damage ◽  
High Dose ◽  
Oxygen Level ◽  
Cellular Automata Model ◽  
Apoptotic Death ◽  
Dose Irradiation

Abstract We investigated the effects of indirect apoptotic cell death due to vascular damage on tumor response to a single large dose with an improved two-dimensional cellular automata model. The tumor growth was simulated by considering the oxygen and nutrients supplied to the tumor through the blood vessels. The cell damage processes were modeled by taking account of the direct cell death and the indirect death due to the radiation-induced vascular damages. The radiation increased the permeation of oxygen and nutrients through the blood vessel or caused the breakdown of the vasculature. The amount of oxygen in cancer cells affected the response of cancer cells to radiation and the tumor growth rate after irradiation. The lack of oxygen led to the apoptotic death of cancer cells. We calculated the tumor control probability (TCP) at different radiation doses, D, the probability of apoptotic death, PO2_ap, the threshold of the oxygen level for indirect apoptotic death, O2t, the average oxygen level in cancer cells, [O2]av, and the vessel survival probability after radiation damage, Pv. Due to the vessel damage, indirect cell death led to a 4% increase in TCP for the dose ranging from 15 Gy to 20 Gy. TCP increased with increasing PO2_ap and O2t due to increased apoptotic death. The variation of TCP as a function of [O2]av exhibited the minimum at [O2]av of 2.7%. The apoptosis increased as [O2]av decreased, leading to an increasing TCP. On the other hand, the direct radiation damage increased, and the apoptosis decreased for higher [O2]av, resulting in a higher TCP. We showed by modeling the radiation damage of blood vessels in a 2D CA simulation that the indirect apoptotic death of cancer cells, caused by the reduction of the oxygen level due to vascular damage after high dose irradiation, increased TCP.

Mixed-ligand copper(ii) Schiff base complexes: the vital role of co-ligands in DNA/protein interactions and cytotoxicity

2017 ◽  
Vol 41 (3) ◽  
pp. 1267-1283 ◽  
Author(s):  
Sellamuthu Kathiresan ◽  
Subramanian Mugesh ◽  
Jamespandi Annaraj ◽  
Maruthamuthu Murugan
Keyword(s):  
Cell Death ◽  
Cell Wall ◽  
Schiff Base ◽  
Protein Interactions ◽  
Apoptotic Cell ◽  
Vital Role ◽  
Mixed Ligand ◽  
Schiff Base Complexes ◽  
Antibacterial Mechanism

Four new mixed-ligand copper(ii) complexes display an antibacterial mechanism of cell death via cell-wall rupture and cytotoxicity via apoptotic cell death.

Role of LFA-1/ICAM-1-dependent cell adhesion in CD40-mediated inhibition of anti-IgM antibody-induced B-cell death

1995 ◽  
Vol 96 (6) ◽  
pp. 1136-1144 ◽  
Author(s):  
M MAYUMI ◽  
S SUMIMOTO ◽  
Y OHSHIMA ◽  
K KATAMURA ◽  
T HEIKE ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Adhesion ◽  
B Cell ◽  
Igm Antibody ◽  
Dependent Cell

scholarly journals Caspase-9 cleavage, do you need it?

2007 ◽  
Vol 405 (1) ◽  
Author(s):  
Davina Twiddy ◽  
Kelvin Cain
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Caspase 9 ◽  
Autocatalytic Cleavage ◽  
Downstream Effector ◽  
Apoptosis Inhibition ◽  
Biochemical Journal ◽  
Effector Caspase ◽  
Effector Caspases

Caspase-9, which is activated by association with the Apaf-1 (apoptotic protease-activating factor-1) apoptosome complex, cleaves and activates the downstream effector caspases-3 and -7, thereby executing the caspase-cascade and cell-death programme. Although caspase-9 does not need to be cleaved to be active, apoptotic cell death is always accompanied by autocatalytic cleavage and by further downstream effector caspase-dependent cleavage of caspase-9. In this issue of the Biochemical Journal, Denault and co-workers evaluate the role of caspase-3-dependent cleavage of caspase-9 and conclude that this mechanism mainly serves to enhance apoptosis by alleviating XIAP (X-linked inhibitor of apoptosis) inhibition of the apical caspase.

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