Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival during avian lip fusion

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4647-4660 ◽  
Author(s):  
Amir M. Ashique ◽  
Katherine Fu ◽  
Joy M. Richman
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Bone Morphogenetic Proteins ◽  
Loss Of Function ◽  
Rapid Induction ◽  
Similar Phenotype ◽  
Primary Palate ◽  
Bmp Signalling ◽  
Frontonasal Mass

Our expression studies of bone morphogenetic proteins (BMPs) and Noggin (a BMP antagonist) in the embryonic chicken face suggested that BMP signals were important for closure of the upper lip or primary palate. We noted that Noggin expression was restricted to the frontonasal mass epithelium but was reduced at the corners of the frontonasal mass (globular processes) just prior to fusion with the adjacent maxillary prominences. We therefore performed gain- and loss-of-function experiments to determine the role of BMPs in lip formation. Noggin treatment led to reduced proliferation and outgrowth of the frontonasal mass and maxillary prominences and ultimately to the deletion of the maxillary and palatine bones. The temporary block in BMP signalling in the mesenchyme also promoted epithelial survival. Noggin treatment also upregulated expression of endogenous BMPs, therefore we investigated whether increasing BMP levels would lead to the same phenotype. A BMP2 bead was implanted into the globular process and a similar phenotype to that produced by Noggin resulted. However, instead of a decrease in proliferation, defects were caused by increased programmed cell death, first in the epithelium and then in the mesenchyme. Programmed cell death was induced primarily in the lateral frontonasal mass with very little cell death medial to the bead. The asymmetric cell death pattern was correlated with a rapid induction of Noggin in the same embryos, with transcripts complementary to the regions with increased cell death. We have demonstrated a requirement for endogenous BMP in the proliferation of facial mesenchyme and that mesenchymal signals promote either survival or thinning of the epithelium. We furthermore demonstrated in vivo that BMP homeostasis is regulated by increasing expression of ligand or antagonist and that such mechanisms may help to protect the embryo from changes in growth factor levels during development or after exposure to teratogens.

scholarly journals "In vivo" toxicity of a truncated version of the Drosophila Rst-IrreC protein is dependent on the presence of a glutamine-rich region in its intracellular domain

2002 ◽  
Vol 74 (2) ◽  
pp. 285-295 ◽  
Author(s):  
RICARDO C. MACHADO ◽  
RODRIGO N.R. PEREIRA ◽  
MARA S.A. COSTA ◽  
RICARDO GUELERMAN P. RAMOS
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Compound Eye ◽  
Carboxyl Terminus ◽  
Loss Of Function ◽  
Rich Region ◽  
Characteristic Wave ◽  
Transmembrane Glycoprotein ◽  
Glutamine Rich Region

The roughest-irregular chiasm C ( rst-irreC) gene of Drosophila melanogaster encodes a transmembrane glycoprotein containing five immunoglobulin-like domains in its extracellular portion and an intracytoplasmic tail rich in serine and threonine as well some conserved motifs suggesting signal transduction activity. In the compound eye, loss-of-function rst-irreC mutants lack the characteristic wave of programmed cell death happening in early pupa and which is essential for the elimination of the surplus interommatidial cells. Here we report an investigation on the role played by the Rst-irreC molecule in triggering programmed cell death. "In vivo" transient expression assays showed that deletion of the last 80 amino acids of the carboxyl terminus produces a form of the protein that is highly toxic to larvae. This toxicity is suppressed if an additional 47 amino acid long, glutamine-rich region ("opa-like domain"), is also removed from the protein. The results suggest the possibility that the opa-like domain and the carboxyl terminus act in concert to modulate rst-irreC function in apoptosis, and we discuss this implication in the context of the general mechanisms causing glutamine-rich neurodegenerative diseases in humans.

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

Retinoic acid regulates programmed cell death through BMP signalling

10.1038/10098 ◽  
1999 ◽  
Vol 1 (2) ◽  
pp. 125-126 ◽  
Author(s):  
J. Rodriguez-Leon ◽  
R. Merino ◽  
D. Macias ◽  
Y. Gañan ◽  
E. Santesteban ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Programmed Cell Death ◽  
Bmp Signalling

scholarly journals An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants

Plant Methods ◽  
2011 ◽  
Vol 7 (1) ◽  
pp. 45 ◽  
Author(s):  
Bridget V Hogg ◽  
Joanna Kacprzyk ◽  
Elizabeth M Molony ◽  
Conor O'Reilly ◽  
Thomas F Gallagher ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Root Hair

scholarly journals Programmed cell death 4 (PDCD4) expression during multistep Barrett's carcinogenesis

2010 ◽  
Vol 63 (8) ◽  
pp. 692-696 ◽  
Author(s):  
Matteo Fassan ◽  
Marco Pizzi ◽  
Giorgio Battaglia ◽  
Luciano Giacomelli ◽  
Paola Parente ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Intestinal Metaplasia ◽  
Negative Regulator ◽  
Pcr Analysis ◽  
Low Grade ◽  
Cytoplasmic Staining ◽  
Programmed Cell Death 4 ◽  
Columnar Metaplasia

AimTo test the contribution of programmed cell death 4 (PDCD4) tumour suppressor gene in Barrett's carcinogenesis.MethodsPDCD4 immunohistochemical expression was assessed in 88 biopsy samples obtained from histologically proven long-segment Barrett's mucosa (BM; 25 non-intestinal columnar metaplasia, 25 intestinal metaplasia (IM), 16 low-grade intraepithelial neoplasia (LG-IEN), 12 high-grade IEN (HG-IEN) and 10 Barrett's adenocarcinoma (BAc)). As controls, 25 additional samples of native oesophageal mucosa (N) were obtained from patients with dyspepsia. To further support the data, the expression levels of miR-21, an important PDCD4 expression regulator, in 14 N, 5 HG-IEN and 11 BAc samples were determined by quantitative real-time PCR analysis.ResultsPDCD4 immunostaining decreased progressively and significantly with the progression of the phenotypic changes occurring during Barrett's carcinogenesis (p<0.001). Normal basal squamous epithelial layers featured strong PDCD4 nuclear immunoreaction (mostly coexisting with weak–moderate cytoplasmic staining). Non-intestinal columnar metaplasia and intestinal metaplasia preserved a strong nuclear immunostaining; conversely, a significant decrease in PDCD4 nuclear expression was seen in dysplastic (LG-IEN and HG-IEN) and neoplastic lesions. Weak–moderate cytoplasmic immunostaining was evident in cases of LG-IEN, while HG-IEN and BAc samples showed weak cytoplasmic or no protein expression. As expected, miR-21 expression was significantly upregulated in HG-IEN and BAc samples, consistently with PDCD4 dysregulation.ConclusionsThese data support a significant role for PDCD4 downregulation in the progression of BM to BAc, and confirm miR-21 as a negative regulator of PDCD4 in vivo. Further efforts are needed to validate PDCD4 as a potential prognostic marker in patients with Barrett's oesophagus.

scholarly journals Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

2012 ◽  
Vol 209 (6) ◽  
pp. 1201-1217 ◽  
Author(s):  
Tadashi Yokosuka ◽  
Masako Takamatsu ◽  
Wakana Kobayashi-Imanishi ◽  
Akiko Hashimoto-Tane ◽  
Miyuki Azuma ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Programmed Cell Death 1

Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1–mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain–containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1–TCR colocalization within microclusters is required for efficient PD-1–mediated suppression. This inhibitory mechanism also functions in PD-1hi T cells generated in vivo and can be overridden by a neutralizing anti–PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation.

scholarly journals The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3247
Author(s):  
Lingxiao Ye ◽  
Zhengxin Zhu ◽  
Xiaochuan Chen ◽  
Haoran Zhang ◽  
Jiaqi Huang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Progression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Escape ◽  
Tumor Treatment

Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

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