scholarly journals Modulation of ERK1/2 activity is crucial for sphingosine-induced death of glioma C6 cells.

2005 ◽  
Vol 52 (4) ◽  
pp. 927-930 ◽  
Author(s):  
Patryk Krzemiński
Keyword(s):  
Cell Death ◽  
Actin Cytoskeleton ◽  
Morphological Changes ◽  
Specific Inhibitor ◽  
Apoptotic Bodies ◽  
C6 Cells ◽  
Glioma C6 ◽  
Shed Light

In this study the contribution of the ERK1/2 pathway to sphingosine-induced death and morphological changes of the actin cytoskeleton in glioma C6 cells was investigated. Surprisingly, the level of ERK1/2 phosphorylation does not change after incubation of cells with sphingosine. Despite this, sphingosine induces rounding and detachment of cells without formation of apoptotic bodies. To shed light on this process, a specific inhibitor of ERK1/2 phosphorylation, U0126, was used. Cells incubated simultaneously with sphingosine and U0126 not only detached, but also exhibited formation of apoptotic-like blebs. These data suggest that during sphingosine-induced glioma C6 cell death apoptotic blebbing is dependent on ERK1/2 signalling and occurs only when ERK1/2 activity is decreased or abolished.

scholarly journals Unleashing the therapeutic potential of apoptotic bodies

2020 ◽  
Vol 48 (5) ◽  
pp. 2079-2088
Author(s):  
Thanh Kha Phan ◽  
Dilara Ceyda Ozkocak ◽  
Ivan Ka Ho Poon
Keyword(s):  
Drug Delivery ◽  
Cell Death ◽  
Therapeutic Potential ◽  
Predictive Biomarkers ◽  
Distinct Type ◽  
Apoptotic Bodies ◽  
Therapeutic Application ◽  
Effector Molecules ◽  
Membrane Bound ◽  
Shed Light

Extracellular vesicles (EVs), membrane-bound vesicles that are naturally released by cells, have emerged as new therapeutic opportunities. EVs, particularly exosomes and microvesicles, can transfer effector molecules and elicit potent responses in recipient cells, making them attractive therapeutic targets and drug delivery platforms. Furthermore, containing predictive biomarkers and often being dysregulated in various disease settings, these EVs are being exploited for diagnostic purposes. In contrast, the therapeutic application of apoptotic bodies (ApoBDs), a distinct type of EVs released by cells undergoing a form of programmed cell death called apoptosis, has been largely unexplored. Recent studies have shed light on ApoBD biogenesis and functions, promisingly implicating their therapeutic potential. In this review, we discuss many strategies to develop ApoBD-based therapies as well as highlight their advantages and challenges, thereby positioning ApoBD for potential EV-based therapy.

Is Necroptosis a Death Pathway in Aluminum-Induced Neuroblastoma Cell Demise?

2008 ◽  
Vol 21 (4) ◽  
pp. 787-796 ◽  
Author(s):  
Q.L. Zhang ◽  
Q. Niu ◽  
X.L. Ji ◽  
P. Conti ◽  
P. Boscolo
Keyword(s):  
Cell Death ◽  
Morphological Changes ◽  
Neuroblastoma Cell ◽  
Specific Inhibitor ◽  
Neural Cell ◽  
Mitochondria Membrane Potential ◽  
Cell Death Pathway ◽  
Apoptosis And Necrosis

Besides being an aggravating factor secondary to major physiological alterations in degenerative diseases, aluminum has also been considered as a risk factor in the etiology. Although many in vivo and in vitro data are in favor of apoptosis and necrosis being involved in Al induced neurodegenerative processes, there is considerable evidence that very complex events may contribute to neural cell death. Necroptosis, a novel cell death pathway, was recently reported to contribute to ischemia brain injury. It is different from, but associated with, apoptosis and necrosis, the two common major pathways of cell demise. In the present study, SH-SY5Y cells were put under stress by Al, a potential degenerative cell death inducer. Nec-1, a specific inhibitor, was used to identify necroptosis. The characteristics observed in Nec-1 and Al treated SH-SY5Y cells showed that necrotic morphological changes were reduced, and a sharp decrease of necrotic rate was detected. Besides, there were Al-induced mitochondria membrane potential decreasing, reactive oxygen species remaining, and autophagosomes declining. The mechanism of Nec-1's effect on cell death may be related to caspases pathways. To our best knowledge, this is the pioneer report on necroptosis in mixed human neural cell death pathways, which might offer a novel therapeutic target for neurodegenerative diseases, and an extended window for neuroprotection.

scholarly journals Effect of Rho-associated kinase inhibition on actin cytoskeleton structure and calcium response in glioma C6 cells.

2006 ◽  
Vol 53 (4) ◽  
pp. 825-831 ◽  
Author(s):  
Berenika Targos ◽  
Paweł Pomorski ◽  
Patryk Krzemiński ◽  
Jolanta Barańska ◽  
Maria Jolanta Redowicz ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Calcium Signaling ◽  
Functional State ◽  
Myosin Ii ◽  
Calcium Signal ◽  
Second Phase ◽  
C6 Cells ◽  
Calcium Response ◽  
Glioma C6 ◽  
Cytoskeleton Reorganization

The role of actin cytoskeleton functional state in glioma C6 cell morphology and calcium signaling was investigated through modification of myosin II activity by blocking Rho-associated kinase with the specific inhibitor Y-27632. Treatment of glioma C6 cells with ROCK inhibitor resulted in actin cytoskeleton reorganization and also in the changed shape and distribution of mitochondria. Changes in the distribution of ER, the main calcium store in glioma C6 cells, were not visible. The inhibition of myosin II activity influences the first phase of calcium signaling evoked by agonist, and both phases of thapsigargin-evoked calcium response. We suggest that the observed increase in Ca2+ release from intracellular stores induced by IP3 formation as well as inhibition of SERCA ATPase is at least in part related to severely affected mitochondria. Enhancement of capacitative calcium entry evoked by thapsigargin is probably associated with the reorganization of the acto-myosin II system. ATP-induced calcium response presents no changes in the second phase. We observed that ATP stimulation of Y-27632 pretreated cells leads to immediate morphological rearrangement of glioma C6 cells. It is a consequence of actin cytoskeleton reorganization: formation of stress fibers and relocation of phosphorylated myosin II to actin filaments. It seems that the agonist-evoked strong calcium signal may be sufficient for myosin II activation and the stress fiber organization. This is the first work showing the dependence between the functional state of the acto-myosin II system and calcium signaling stressing the reversible character of this relationship.

scholarly journals Is MLC phosphorylation essential for the recovery from ROCK inhibition in glioma C6 cells?

2011 ◽  
Vol 58 (1) ◽  
Author(s):  
Jarosław Korczyński ◽  
Katarzyna Sobierajska ◽  
Patryk Krzemiński ◽  
Anna Wasik ◽  
Dorota Wypych ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Morphology ◽  
C6 Cells ◽  
Cytoskeleton Organization ◽  
Glioma C6 ◽  
Cytoskeleton Reorganization ◽  
Actin Cytoskeleton Organization ◽  
Rock Inhibition ◽  
Cytoskeleton Dynamics ◽  
Mlc Phosphorylation

Inhibition of Rho-associated protein kinase (ROCK) activity in glioma C6 cells induces changes in actin cytoskeleton organization and cell morphology similar to those observed in other types of cells with inhibited RhoA/ROCK signaling pathway. We show that phosphorylation of myosin light chains (MLC) induced by P2Y₂ receptor stimulation in cells with blocked ROCK correlates in time with actin cytoskeleton reorganization, F-actin redistribution and stress fibers assembly followed by recovery of normal cell morphology. Presented results indicate that myosin light-chain kinase (MLCK) is responsible for the observed phosphorylation of MLC. We also found that the changes induced by P2Y₂ stimulation in actin cytoskeleton dynamics and morphology of cells with inhibited ROCK, but not in the level of phosphorylated MLC, depend on the presence of calcium in the cell environment.

scholarly journals Regulation of membrane release in apoptosis

1998 ◽  
Vol 334 (2) ◽  
pp. 479-485 ◽  
Author(s):  
Jiandi ZHANG ◽  
Timothy A. DRISCOLL ◽  
Yusuf A. HANNUN ◽  
Lina M. OBEID
Keyword(s):  
Cell Death ◽  
Membrane Lipids ◽  
Morphological Changes ◽  
Membrane Vesicles ◽  
Heterogeneous Population ◽  
Apoptotic Bodies ◽  
Fundamental Process ◽  
Release Assay ◽  
Lymphoid Cell Lines

Apoptosis is a fundamental process of cell regulation whereby cells execute one or more biochemical programs leading to cell death. Several mechanisms have been evaluated and suggested to play roles in the regulation of apoptosis, including the activation of phospholipase A2 (PLA2), usually measured as release of 3H-labelled arachidonic acid (AA) from prelabelled cells. The current study was aimed at examining the role of PLA2 in regulating apoptosis in response to several inducers (such as vincristine and etoposide) in lymphoid cell lines. Cells were labelled with [3H]fatty acids and the released radioactivity was characterized. These studies indicated that the AA release assay did not reflect release of non-esterified fatty acid via activation of the PLA2 pathway. Rather, studies using TLC and electron microscopy showed that AA release reflected a previously unsuspected shedding of a heterogeneous population of membrane vesicles and fragments, probably as components of apoptotic bodies. Further studies demonstrated that this process is an integral part of apoptosis. Overexpression of Bcl-2 or the addition of caspase peptide inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethane prevented the characteristic morphological changes of cell death, and completely inhibited the release of membrane vesicles and fragments. On the other hand, release of membrane vesicles and fragments was caused by various inducers of apoptosis, as measured by release of either 3H-labelled AA or palmitic acid. Thus the present study demonstrates that the release of membrane lipids during apoptosis defines a new assay for apoptosis and has allowed the investigation of the mechanisms regulating formation of apoptotic bodies.

Cell death (apoptosis) during pancreatic involution after raw soya flour feeding in the rat

1986 ◽  
Vol 250 (1) ◽  
pp. G9-G14 ◽  
Author(s):  
P. S. Oates ◽  
R. G. Morgan ◽  
A. M. Light
Keyword(s):  
Cell Death ◽  
Acinar Cell ◽  
Morphological Changes ◽  
Acinar Cells ◽  
Normal Diet ◽  
Soya Flour ◽  
Apoptotic Bodies ◽  
Dna And Rna

Involution of the enlarged pancreas was studied in rats changed from a diet of raw soya flour (RSF) to a normal diet of cubes. After feeding RSF for 4 or 12 wk pancreatic weight, DNA, RNA, and protein were all significantly greater than in control animals fed cubes continuously. When these animals were changed to a cube diet, pancreatic DNA and RNA returned to control values within 48 h, while pancreatic weight and protein reverted to control values within 7 days of the change in diet. The morphological changes seen in the pancreas during involution indicate that cell death occurred by the process of apoptosis. Increased cell death during involution was seen as a rapid increase in the incidence of apoptotic bodies (AB) located in the cytoplasm of intact acinar cells and macrophages. These AB's contained condensed fragments of cytoplasm, nuclear, or a combination of these remnants, which were derived from the acinar cell. The increase in apoptosis after withdrawal of the RSF diet was probably in response to the withdrawal of the trophic influence, cholecystokinin.

Role of the actin cytoskeleton in store-mediated calcium entry in glioma C6 cells

2002 ◽  
Vol 296 (2) ◽  
pp. 484-491 ◽  
Author(s):  
Paweł Sabała ◽  
Berenika Targos ◽  
Antonella Caravelli ◽  
Rafał Czajkowski ◽  
Dmitri Lim ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Calcium Entry ◽  
C6 Cells ◽  
Glioma C6

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

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