Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis‐ and autophagy‐associated molecules

Sahar M. Gebril; Yuko Ito; Masa‐Aki Shibata; Kentaro Maemura; Eman E. Abu‐Dief; Mahmoud R. A. Hussein; Usama M. Abdelaal; Hoda M. Elsayed; Yoshinori Otsuki; Kazuhide Higuchi

doi:10.1111/iep.12370

Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions

10.26434/chemrxiv.5382781.v1 ◽

2017 ◽

Author(s):

Ellen Sletten ◽

Rachael A. Day ◽

Daniel A. Estabrook ◽

Jessica K. Logan

Keyword(s):

Cell Death ◽

Photodynamic Therapy ◽

Induce Cell Death ◽

Perfluorocarbon Nanoemulsions

<p>Photodynamic therapy (PDT) requires photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT. </p>

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Faculty Opinions recommendation of Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by Helicobacter pylori infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14256973.15768101 ◽

2012 ◽

Author(s):

Ian Beales

Keyword(s):

Helicobacter Pylori ◽

Acid Secretion ◽

Parietal Cells ◽

Helicobacter Pylori Infection ◽

Gastric Parietal Cells

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Faculty Opinions recommendation of Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.724152373.793504124 ◽

2015 ◽

Author(s):

Padmini Salgame ◽

Archana Gopalakrishnan

Keyword(s):

Cell Death ◽

Mycobacterium Tuberculosis ◽

Vaccine Candidate ◽

Induce Cell Death

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La3+ and pH sensitivity of Ca2+ entry and intracellular store filling in gastric parietal cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.269.5.g770 ◽

1995 ◽

Vol 269 (5) ◽

pp. G770-G778 ◽

Cited By ~ 2

Author(s):

P. A. Negulescu ◽

T. E. Machen

Keyword(s):

Positive Feedback ◽

Low Ph ◽

Parietal Cells ◽

Additional Increase ◽

Cholinergic Agonist ◽

Intracellular Store ◽

Entry Pathway ◽

Signaling Function ◽

Previously Treated ◽

Gastric Parietal Cells

The fluorescent Ca2+ indicator fura 2 was used to measure cytosolic free [Ca2+] ([Ca2+]i) in order to obtain information about relative rates of Ca2+ influx into parietal cells during treatment with carbachol (a cholinergic agonist) or thapsigargin (TG, a Ca(2+)-mobilizing agent) or during reloading of the internal Ca2+ stores. In Ca(2+)-containing solutions, carbachol-, TG-, and reloading-stimulated Ca2+ entry exhibited nearly identical sensitivity to La3+ [inhibition constant (Ki) approximately 10 microM] or low pH (pKi approximately 7.0). In experiments in which carbachol and TG were used, there was no additional increase in [Ca2+]i when TG was added to carbachol-treated cells or when carbachol was added to cells previously treated with TG. Thus it is likely that a single Ca2+ entry pathway serves a signaling function as well as a role in refilling the Ca2+ store during reloading. Because the Ca2+ pathway is exquisitely sensitive to pH and serosal pH increases during stimulant-induced H+ secretion (which is activated by increases in [Ca2+]i), this mechanism will exert positive feedback on parietal cells in the intact stomach. When parietal cells were pretreated with carbachol in Ca(2+)-free solutions, reloading was independent of pH and La3+, suggesting that Ca(2+)-containing solutions should be used to determine the properties of the influx pathway.

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Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation

Cell Death and Disease ◽

10.1038/s41419-021-04050-7 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Viktorija Juric ◽

Lance Hudson ◽

Joanna Fay ◽

Cathy E. Richards ◽

Hanne Jahns ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Cell Cycle Arrest ◽

Cortical Neurons ◽

Apoptotic Cell ◽

Cdk Inhibitors ◽

Induce Cell Death ◽

Viability Loss ◽

Cycle Arrest ◽

Recurrent Gbm

AbstractActivation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation or overexpression of CDKs can support tumourigenesis including glioblastoma (GBM), the most common and aggressive primary brain tumour in adults. The incurability of GBM highlights the need to discover novel and more effective treatment options. Since CDKs 2, 7 and 9 were found to be overexpressed in GBM, we tested the therapeutic efficacy of two CDK inhibitors (CKIs) (CYC065 and THZ1) in a heterogeneous panel of GBM patient-derived cell lines (PDCLs) cultured as gliomaspheres, as preclinically relevant models. CYC065 and THZ1 treatments suppressed invasion and induced viability loss in the majority of gliomaspheres, irrespective of the mutational background of the GBM cases, but spared primary cortical neurons. Viability loss arose from G2/M cell cycle arrest following treatment and subsequent induction of apoptotic cell death. Treatment efficacies and treatment durations required to induce cell death were associated with proliferation velocities, and apoptosis induction correlated with complete abolishment of Mcl-1 expression, a cell cycle-regulated antiapoptotic Bcl-2 family member. GBM models generally appeared highly dependent on Mcl-1 expression for cell survival, as demonstrated by pharmacological Mcl-1 inhibition or depletion of Mcl-1 expression. Further analyses identified CKI-induced Mcl-1 loss as a prerequisite to establish conditions at which the BH3-only protein Bim can efficiently induce apoptosis, with cellular Bim amounts strongly correlating with treatment efficacy. CKIs reduced proliferation and promoted apoptosis also in chick embryo xenograft models of primary and recurrent GBM. Collectively, these studies highlight the potential of these novel CKIs to suppress growth and induce cell death of patient-derived GBM cultures in vitro and in vivo, warranting further clinical investigation.

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Receptor-operated Ca2+ channels in gastric parietal cells: gastrin and carbachol induce Ca2+ influx in depleting intracellular Ca2+ stores

Biochemical Journal ◽

10.1042/bj2890117 ◽

1993 ◽

Vol 289 (1) ◽

pp. 117-124 ◽

Cited By ~ 10

Author(s):

S Roche ◽

J P Bali ◽

R Magous

Keyword(s):

Steady State ◽

Receptor Activation ◽

Parietal Cells ◽

The Other ◽

Bivalent Cation ◽

Gtp Binding ◽

Gastric Parietal Cells ◽

Type Receptor ◽

Ca2 Channels ◽

Stimulation Of

The mechanism whereby gastrin-type receptor and muscarinic M3-type receptor regulate free intracellular Ca2+ concentration ([Ca2+]i) was studied in rabbit gastric parietal cells stimulated by either gastrin or carbachol. Both agonists induced a biphasic [Ca2+]i response: a transient [Ca2+]i rise, followed by a sustained steady state depending on extracellular Ca2+. Gastrin and carbachol also caused a rapid and transient increase in Mn2+ influx (a tracer for bivalent-cation entry). Pre-stimulation of cells with one agonist drastically decreased both [Ca2+]i increase and Mn2+ influx induced by the other. Neither diltiazem nor pertussistoxin treatment had any effect on agonist-stimulated Mn2+ entry. Thapsigargin, a Ca(2+)-pump inhibitor, induced a biphasic [Ca2+]i increase, and enhanced the rate of Mn2+ entry. Preincubation of cells with thapsigargin inhibits the [Ca2+]i increase as well as Mn2+ entry stimulated by gastrin or by carbachol. Thapsigargin induced a weak but significant increase in Ins(1,4,5)P3 content, but this agent had no effect on the agonist-evoked Ins(1,4,5)P3 response. In permeabilized parietal cells, Ins(1,4,5)P3 and caffeine caused an immediate Ca2+ release from intracellular pools, followed by a reloading of Ca2+ pools which can be prevented in the presence of thapsigargin. We conclude that (i) gastrin and carbachol mobilize common Ca2+ intracellular stores, (ii) Ca2+ permeability secondary to receptor activation involves neither a voltage-sensitive Ca2+ channel nor a GTP-binding protein from the G1 family, and (iii) agonists regulate common Ca2+ channels in depleting intracellular Ca2+ stores.

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