scholarly journals Induction of tissue transglutaminase by dexamethasone: its correlation to receptor number and transglutaminase-mediated cell death in a series of malignant hamster fibrosarcomas

1998 ◽  
Vol 331 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Timothy S. JOHNSON ◽  
Claire I. SCHOLFIELD ◽  
James PARRY ◽  
Martin GRIFFIN
Keyword(s):  
Cell Death ◽  
Cell Damage ◽  
Tissue Transglutaminase ◽  
Receptor Protein ◽  
Mrna Synthesis ◽  
Body Formation ◽  
Transglutaminase Activity ◽  
Receptor Number ◽  
Dose Dependent ◽  
Hamster Fibrosarcoma

Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21 hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity, which can be correlated with dexamethasone-responsive receptor numbers in each cell line. Increasing the number of dexamethasone-responsive receptors by transfection of cells with the HG1 glucocorticoid receptor protein caused an increase in transglutaminase activity that was proportional to the level of transfected receptor. In all experiments the levels of the tissue transglutaminase-mediated detergent-insoluble bodies was found to be comparable with increases in transglutaminase activity. Despite an increase in detergent-insoluble body formation, an increase in apoptosis as measured by DNA fragmentation was not found. Incubation of cells with the non-toxic competitive transglutaminase substrate fluorescein cadaverine led to the incorporation of this fluorescent amine into cellular proteins when cells were damaged after exposure to trypsin during cell passage. These cross-linked proteins containing fluorescein cadaverine were shown to be present in the detergent-insoluble bodies, indicating that the origin of these bodies is via activation of tissue transglutaminase after cell damage by trypsinization rather than apoptosis per se,since Met B cells expressing the bcl-2 cDNA were not protected from detergent-insoluble body formation. We describe a novel mechanism of cell death related to tissue transglutaminase expression and cell damage.

Downregulation of the PTH/PTHrP receptor by vitamin D3 in the osteoblast-like ROS 17/2.8 cells

1996 ◽  
Vol 270 (4) ◽  
pp. E654-E660 ◽  
Author(s):  
L. Y. Xie ◽  
A. Leung ◽  
G. V. Segre ◽  
I. Yamamoto ◽  
A. B. Abou-Samra
Keyword(s):  
Receptor Gene ◽  
Inhibitory Effect ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Dihydroxyvitamin D3 ◽  
Low Concentrations ◽  
Potent Inhibitory Effect ◽  
Receptor Number ◽  
Pthrp Receptor ◽  
Dose Dependent

Effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the expression of the parathyroid hormone (PTH)/PTH-related peptide (rP) receptor protein and mRNA in ROS 17/2.8 cells were studied. Treatment of ROS 17/2.8 cells with 1,25(OH)2D3 caused time- and dose-dependent suppression of PTH/PTHrP receptor number and immunoreactivity. The effects required more than 24 h incubation with 1,25(OH)2D3 and were maximal by 72 h. The cells did not recover their PTH/PTHrP receptors even after 4 days of treatment with control medium. Treatment with low concentrations of 1,25(OH)2D3 (0.1 M) dramatically decreased the PTH/PTHrP receptor mRNA levels, which were maximal after 24 h of incubation. The half-life of the PTH/PTHrP receptor transcript, 6-8 h, was similar in control and 1,25(OH)2D3-treated cells, suggesting that 1,25(OH)2D3 acts in controlling transcription of the PTH/PTHrP receptor gene but does not change the degradation rate of the PTH/PTHrP receptor transcripts. These data indicate that 1,25(OH)2D3 has a potent inhibitory effect on the expression of the PTH/PTHrP receptor protein and mRNA in ROS 17/2.8 cells.

Tumor Cell Death Induced through the Receptor for Interleukin-2

1995 ◽  
Vol 8 (3) ◽  
pp. 161-172
Author(s):  
G. Migliorati ◽  
D. V. Delfino ◽  
G. Nocentini ◽  
I. Nicoletti ◽  
C. Riccardi
Keyword(s):  
Cell Death ◽  
Interleukin 2 ◽  
Mrna Synthesis ◽  
Tumor Cell Death ◽  
Neoplastic Cells ◽  
Dependent Inhibition ◽  
Apoptotic Effect ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

We performed experiments to analyze the possible apoptotic effect of recombinant IL-2 on neoplastic cells expressing the receptor for IL-2. YAC-1 or EL/4 tumor cells, incubated in vitro with IL-2 or with monoclonal antibodies against the alfa-chain of the IL-2 receptor, underwent to apoptosis as analyzed by reduction in nuclear size, derangement in chromatin structure and DNA fragmentation in oligonucleosomal subunits. The apoptotic phenomenon was time- and dose-dependent. Inhibition of mRNA synthesis D-act or addition of IL-4 counteracted the effect of both IL-2 and anti-IL-2/r antibodies. Both rIL-2 or anti-IL-2/r mAb determined an augmentation of phosphorilation pattern as measured by western immunoblotting, and a transient augmentation of Ca++ as evaluated by a spectrophotometrical assay. These data suggest that stimulation of IL-2 receptor may induce an active process of cell death on neoplastic cells in vitro.

Alpha-Tocopherol Protects Cultured Human Cells from the Acute Lethal Cytotoxicity of Dioxin

2002 ◽  
Vol 72 (3) ◽  
pp. 147-153 ◽  
Author(s):  
Kei-Ichi Hirai ◽  
Jie-Hong Pan ◽  
Ying-Bo Shui ◽  
Eriko Simamura ◽  
Hiroki Shimada ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Damage ◽  
Smooth Endoplasmic Reticulum ◽  
Dehydroascorbic Acid ◽  
Human Cells ◽  
Alpha Tocopherol ◽  
Cervical Cancer Cells ◽  
Cultured Human Cells ◽  
Nuclear Damage ◽  
Conjunctival Epithelial Cells

The possible protection of cultured human cells from acute dioxin injury by antioxidants was investigated. The most potent dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), caused vacuolization of the smooth endoplasmic reticulum and Golgi apparatus in cultured human conjunctival epithelial cells and cervical cancer cells. Subsequent nuclear damage included a deep irregular indentation resulting in cell death. A dosage of 30–40 ng/mL TCDD induced maximal intracellular production of H2O2 at 30 minutes and led to severe cell death (0–31% survival) at two hours. A dose of 1.7 mM alpha-tocopherol or 1 mM L-dehydroascorbic acid significantly protected human cells against acute TCDD injuries (78–97% survivals), but vitamin C did not provide this protection. These results indicate that accidental exposure to fatal doses of TCDD causes cytoplasmic free radical production within the smooth endoplasmic reticular systems, resulting in severe cytotoxicity, and that vitamin E and dehydroascorbic acid can protect against TCDD-induced cell damage.

Inhibition of Autophagy Potentiated Hippocampal Cell Death Induced by Endoplasmic Reticulum Stress and its Activation by Trehalose Failed to be Neuroprotective

2019 ◽  
Vol 16 (1) ◽  
pp. 3-11
Author(s):  
Luisa Halbe ◽  
Abdelhaq Rami
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Damage ◽  
Protective Mechanism ◽  
Unfolded Proteins ◽  
Neuronal Viability ◽  
Hippocampal Cell ◽  
Trigger Cell Death ◽  
Autophagy Inhibition

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

Synthesis, Spectral Characterization, Antibacterial and Anticancer Activity of some Titanium Complexes

2018 ◽  
Vol 18 (5) ◽  
pp. 739-746 ◽  
Author(s):  
Raj Kaushal ◽  
Nitesh Kumar ◽  
Archana Thakur ◽  
Kiran Nehra ◽  
Pamita Awasthi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Spectral Characterization ◽  
Mechanistic Study ◽  
Titanium Complexes ◽  
G0 Phase ◽  
Antibacterial And Anticancer Activity ◽  
Dose Dependent

Abstract: Background: After the discovery of cisplatin, first non platinum anticancer drugs having excellent efficacy were budotitane and TiCl2(cp)2 but action mechanism is not clear. Therefore, we hereby reporting synthesis and biological activities novel titanium complexes to explore their mode of action. Objectives: Synthesis, spectral characterization, antibacterial and anticancer activity of some titanium complexes. Antibacterial studies on various bacterial strains and anticancer studies on HeLa, C6, CHO cancerous cell lines have been performed. Further, the cell death mechanistic study was done on CHO cell lines. Method: Titanium complexes with and without labile groups have been synthesized by reacting of TiCl4 with nitrogen containing ligands viz. 1,2-diaminocyclohexane, 1,10-Phenanthroline, adamantylamine, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine in predetermined molar ratios. Antibacterial and anticancer studies were performed by agar well diffusion method and MTT assay respectively. Cell cycle analysis is done by using flow cytometry. Results: Complex 2 i.e TiCl2(Phen)2 showed better activity than other complexes as an antibacterial as well as anticancer agent. Phase contrast imaging indicates that observed morphological changes of cells was dose dependent. Cell death mechanistic study have shown the increase in sub G0 phase population as well as formation of blebbing and fragmentation of chromatin material which is an indicative measure of apoptosis. Conclusion: Complex 2 proved to be more effective bactericide and cytotoxic agent. Cell cycle analysis showed cell arrest in G0 phase. Apoptosis percentage was found to increase in a dose dependent manner. So, prepared titanium complexes can be put to use as an important chemotherapeutic agents.

Parathyroid Ca2+-conducting currents are modulated by muscarinic receptor agonists and antagonists

1997 ◽  
Vol 273 (5) ◽  
pp. E880-E890 ◽  
Author(s):  
Wenhan Chang ◽  
Tsui-Hua Chen ◽  
Stacy A. Pratt ◽  
Benedict Yen ◽  
Michael Fu ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Inositol Phosphate ◽  
Receptor Protein ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Pipette Solution ◽  
Pcr Products ◽  
Inositol Phosphate Accumulation ◽  
Receptor Cdna ◽  
Dose Dependent

Parathyroid cells express Ca2+-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration ≈10−8 M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution. (+)-Muscarine enhanced the adenosine 3′,5′-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed >90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.

Nano-CuO causes cell damage through activation of dose-dependent autophagy and mitochondrial lncCyt b-AS/ND5-AS/ND6-AS in SH-SY5Y cells

2021 ◽  
pp. 1-38
Author(s):  
Zhanqiang Du ◽  
Xueqing Chai ◽  
Xiaolin Li ◽  
Guogang Ren ◽  
Xiuyi Yang ◽  
...  
Keyword(s):  
Cell Damage ◽  
Dose Dependent

scholarly journals Apoptosis and inflammation

1995 ◽  
Vol 4 (1) ◽  
pp. 5-15 ◽  
Author(s):  
C. Haanen ◽  
I. Vermes
Keyword(s):  
Cell Death ◽  
Inflammatory Reaction ◽  
Inflammatory Diseases ◽  
Apoptotic Cell ◽  
Cell Damage ◽  
Target Cells ◽  
Apoptotic Bodies ◽  
Accidental Injury ◽  
Inflammatory Reactions ◽  
Inflammatory Processes

During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972) introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases.

scholarly journals Cytotoxic Influence of Khat (Catha edulis (Vahl) Forssk. ex Endl) on Oral Fibroblasts, Squamous Carcinoma Cells, and Expression of α Smooth Muscle Actin

2021 ◽  
Vol 11 (8) ◽  
pp. 3524
Author(s):  
Azeem Ul Yaqin Syed ◽  
Muhammad A. Ahmed ◽  
Eman I. AlSagob ◽  
Mansour Al-Askar ◽  
Abdulrahman M. AlMubarak ◽  
...  
Keyword(s):  
Cell Death ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Control Cell ◽  
Squamous Carcinoma ◽  
Carcinoma Cells ◽  
Muscle Actin ◽  
Catha Edulis ◽  
Squamous Carcinoma Cells ◽  
Dose Dependent

The aim was to determine the cytotoxicity of Khat (Catha edulis (Vahl) Forssk. ex Endl) on normal oral fibroblasts (NOFs) and SCC4 (squamous carcinoma cells) along with expression of α-smooth muscle actin (α-SMA) in fibroblasts. Khat filtrate was prepared to obtain a concentrated viscous solution. NOFs and SCC4 cells were cultured in biological cabinets and were grown in Dulbeccos’ modified Eagles medium. Frozen cells were thawed at 37 °C and cell seeding was performed. NOFs and SCC4 cells were seeded on 96 well plates and allowed to attach. The medium was removed and a fresh medium containing different concentrations of Khat was added. The group without Khat served as a negative control and 4% paraformaldehyde as the positive control. Cell viability was assessed using the MTT assay and effect of Khat on fibroblast and SCC4 phenotypes was evaluated by immunostaining. Analysis of variance was used to assess data (p < 0.05). NOF 316 showed cell death in response to 4% paraformaldehyde, 12.5, 6.25, and 3.12 mg/mL of Khat. The highest concentration of Khat (25 mg/mL) failed to cause cytotoxicity of NOF 316. NOF 319 and NOF 26 displayed cell death at all concentrations of Khat, however, cytotoxicity was not dose dependent. NOF 18 and SCC4 cells showed dose-dependent cell death. NOF 316 showed α-SMA expression after 1 mg/mL of Khat exposure. Not all fibroblasts were α-SMA-positive, suggesting specific activation of a subset of fibroblasts. Khat is cytotoxic to NOF and SCC4 cells. Furthermore, it can also cause activation and phenotypic changes in oral fibroblasts, indicating a potential role in progression of oral squamous cell carcinoma.

Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development

2002 ◽  
Vol 282 (3) ◽  
pp. L477-L483 ◽  
Author(s):  
Cédric Luyet ◽  
Peter H. Burri ◽  
Johannes C. Schittny
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Lung Development ◽  
Structural Changes ◽  
Tissue Transglutaminase ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Morphological Criteria ◽  
Postnatal Lung Development

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1–0.01 μg/g, days 1–4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19–21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa ( day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.

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