scholarly journals OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific Manner

1998 ◽  
Vol 141 (6) ◽  
pp. 1407-1414 ◽  
Author(s):  
Alfonso Dueñas Gonzalez ◽  
Mitsunori Kaya ◽  
Wen Shi ◽  
Howard Song ◽  
Joseph R. Testa ◽  
...  

OCI-5/GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the cell surface through a glycosyl-phosphatidylinositol anchor. It has recently been shown that the OCI-5/GPC3 gene is mutated in patients with the Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked disorder characterized by pre- and postnatal overgrowth and various visceral and skeletal dysmorphisms. Some of these dysmorphisms could be the result of deficient growth inhibition or apoptosis in certain cell types during development. Here we present evidence indicating that OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma (II14) and breast cancer (MCF-7). This induction, however, is cell line specific since it is not observed in NIH 3T3 fibroblasts or HT-29 colorectal tumor cells. We also show that the apoptosis-inducing activity in II14 and MCF-7 cells requires the anchoring of OCI-5/GPC3 to the cell membrane. The glycosaminoglycan chains, on the other hand, are not required. MCF-7 cells can be rescued from OCI-5/GPC3–induced cell death by insulin-like growth factor 2. This factor has been implicated in Beckwith-Wiedemann, an overgrowth syndrome that has many similarities with SGBS. The discovery that OCI-5/GPC3 is able to induce apoptosis in a cell line– specific manner provides an insight into the mechanism that, at least in part, is responsible for the phenotype of SGBS patients.

1992 ◽  
Vol 12 (4) ◽  
pp. 1864-1871 ◽  
Author(s):  
G Q Daley ◽  
R A Van Etten ◽  
P K Jackson ◽  
A Bernards ◽  
D Baltimore

N-terminal myristoylation can promote the association of proteins with the plasma membrane, a property that is required for oncogenic variants of Src and Abl to transform fibroblastic cell types. The P210bcr/abl protein of chronic myelogenous leukemia cells is not myristoylated and does not stably transform NIH 3T3 fibroblasts; however, it will transform lymphoid and myeloid cell types in vitro and in vivo, suggesting that myristoylation is not required for Abl variants to transform hematopoietic cells. To test this hypothesis, we introduced point mutations that disrupt myristoylation into two activated Abl proteins, v-Abl and a deletion mutant of c-Abl (delta XB), and examined their ability to transform an interleukin-3-dependent lymphoblastoid cell line, Ba/F3. Neither of the nonmyristoylated Abl proteins transformed NIH 3T3 fibroblasts, but like P210bcr/abl, both were capable of transforming the Ba/F3 cells to factor independence and tumorigenicity. Nonmyristoylated Abl variants did not associate with the plasma membrane in the transformed Ba/F3 cells. These results demonstrate that Abl proteins can transform hematopoietic cells in the absence of membrane association and suggest that distinct functions of Abl are required for transformation of fibroblast and hematopoietic cell types.


1989 ◽  
Vol 259 (3) ◽  
pp. 737-741 ◽  
Author(s):  
M J O Wakelam

The stimulation of inositol phosphate generation in NIH-3T3 cells and a derived transformant overexpressing the p21N-ras gene (T15+ cells) was examined. Incubation with NaF in the presence of Al3+ leads to the generation of inositol phosphates in each cell type, though the response in the T15+ cells is significantly amplified. The effect of fluoroaluminate is dose- and time-dependent. No differences were observed in fluoroaluminate-stimulated cyclic AMP accumulation among the cell types. In another NIH-3T3-derived cell line that expresses the transforming lys61 mutant of N-ras, no amplification of fluoroaluminate-stimulated inositol phosphate generation is observed. These results provide support for the proposal that, in the T15 cell line, p21N-ras can act in a guanine nucleotide-binding regulatory protein (G-protein)-like manner.


1992 ◽  
Vol 12 (4) ◽  
pp. 1864-1871
Author(s):  
G Q Daley ◽  
R A Van Etten ◽  
P K Jackson ◽  
A Bernards ◽  
D Baltimore

N-terminal myristoylation can promote the association of proteins with the plasma membrane, a property that is required for oncogenic variants of Src and Abl to transform fibroblastic cell types. The P210bcr/abl protein of chronic myelogenous leukemia cells is not myristoylated and does not stably transform NIH 3T3 fibroblasts; however, it will transform lymphoid and myeloid cell types in vitro and in vivo, suggesting that myristoylation is not required for Abl variants to transform hematopoietic cells. To test this hypothesis, we introduced point mutations that disrupt myristoylation into two activated Abl proteins, v-Abl and a deletion mutant of c-Abl (delta XB), and examined their ability to transform an interleukin-3-dependent lymphoblastoid cell line, Ba/F3. Neither of the nonmyristoylated Abl proteins transformed NIH 3T3 fibroblasts, but like P210bcr/abl, both were capable of transforming the Ba/F3 cells to factor independence and tumorigenicity. Nonmyristoylated Abl variants did not associate with the plasma membrane in the transformed Ba/F3 cells. These results demonstrate that Abl proteins can transform hematopoietic cells in the absence of membrane association and suggest that distinct functions of Abl are required for transformation of fibroblast and hematopoietic cell types.


2018 ◽  
Vol 11 (3) ◽  
pp. 204-208
Author(s):  
Ivana Šušaníková ◽  
Adriána Kvasnicová ◽  
Žofia Brzková ◽  
Ondrej Ďuriška ◽  
Pavel Mučaji

Abstract The aim of the research was to determine some basic biological activities of less biomedically studied but commonly known two fungi from the Boletaceae family Suillellus rubrosanguineus and Tylopilus felleus, which grow in the forests of Middle Europe. The cytotoxicity tests of the ethanol and chloroform extracts were carried out using NIH-3T3 and MCF-7 cell lines. The presence of alkaloids in the extracts was assessed by the reaction with Dragendorff reagent. In all of the extracts the positive reaction with the reagent was observed. In general, the extracts from Suillellus rubrosanguineus were more cytotoxic than the extracts from Tylopilus felleus and exhibited no selectivity of activities on healthy and cancer cell lines. However, the extracts from Tylopilus felleus proved to be selectively cytotoxic for cancer cell line. Tylopilus extracts or their isolated bioactive compounds could be considered for further study in pre-clinical experiments.


1999 ◽  
Vol 291 (4) ◽  
pp. 224-231 ◽  
Author(s):  
H. Sakai ◽  
Noriaki Toyota ◽  
Fumihiko Ito ◽  
Hidetoshi Takahashi ◽  
Yoshio Hashimoto ◽  
...  

1985 ◽  
Vol 101 (4) ◽  
pp. 1442-1454 ◽  
Author(s):  
P Cowin ◽  
H P Kapprell ◽  
W W Franke

Desmosomal plaque proteins have been identified in immunoblotting and immunolocalization experiments on a wide range of cell types from several species, using a panel of monoclonal murine antibodies to desmoplakins I and II and a guinea pig antiserum to desmosomal band 5 protein. Specifically, we have taken advantage of the fact that certain antibodies react with both desmoplakins I and II, whereas others react only with desmoplakin I, indicating that desmoplakin I contains unique regions not present on the closely related desmoplakin II. While some of these antibodies recognize epitopes conserved between chick and man, others display a narrow species specificity. The results show that proteins whose size, charge, and biochemical behavior are very similar to those of desmoplakin I and band 5 protein of cow snout epidermis are present in all desmosomes examined. These include examples of simple and pseudostratified epithelia and myocardial tissue, in addition to those of stratified epithelia. In contrast, in immunoblotting experiments, we have detected desmoplakin II only among cells of stratified and pseudostratified epithelial tissues. This suggests that the desmosomal plaque structure varies in its complement of polypeptides in a cell-type specific manner. We conclude that the obligatory desmosomal plaque proteins, desmoplakin I and band 5 protein, are expressed in a coordinate fashion but independently from other differentiation programs of expression such as those specific for either epithelial or cardiac cells.


2006 ◽  
Vol 84 (5) ◽  
pp. 774-779 ◽  
Author(s):  
Tetsuya Tanaka ◽  
Shin Murakami ◽  
Haruto Kumura ◽  
Ikuo Igarashi ◽  
Kei-ichi Shimazaki

Toxoplasma gondii is an obligatory intracellular parasitic protozoan transmitted via the ingestion of raw, infected meat that causes congenital infections. In a cell-free environment, virulent Toxoplasma was strikingly resistant to H2O2. The activity of H2O2 or H2O2 generated by glucose – glucose oxidase against the resistant tachyzoite stage of pathogenic T. gondii was enhanced by adding KI and bovine lactoperoxidase (bLPO), referred to here as the bLPO system. Replacing bLPO (heme content, 90%) with recombinant bLPO (heme content, 6%) did not enhance the parasiticidal activity with KI and H2O2. These results indicated that heme contributed to the enzyme activity and resulted in the killing of tachyzoites of T. gondii. Tachyzoites treated with the bLPO system also lost the ability to penetrate the mouse fibroblast cell line (NIH/3T3), and could be killed intracellularly after exposure by bLPO to a mouse macrophage cell line (J774A.1). These findings suggested that toxicity was mediated through small amounts of H2O2 generated by phagocytic events in naive macrophages, and by the peroxidative activity of bLPO. Our observations suggest that the bLPO system could help prevent the development of Toxoplasmosis in humans after ingesting raw, infected meat.


2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.


Author(s):  
Philip D. Lunger ◽  
H. Fred Clark

Cell line VSW, derived from the spleen of a tumor-bearing Asian pit viper, spontaneously produces C-type virions budding from membranes, and similar virions that develop within mitochondria. Rabies virus has been determined to replicate more efficiently in VSW cells than in a variety of other cell types cultivated from reptiles, amphibians or fish. We have compared the morphology of three strains (CVS, ERA and HEP) of fixed BHK/21 cell-adapted rabies virus in VSW cells infected at a cell multiplicity of infection of 20 and incubated at 33&C for 8 days prior to fixation.


1992 ◽  
Vol 283 (2) ◽  
pp. 347-354 ◽  
Author(s):  
T Fu ◽  
Y Okano ◽  
Y Nozawa

Bradykinin (BK) induced a biphasic increase in 1,2-diacylglycerol (DAG) in both K-ras-transformed fibroblasts (DT) and the parent NIH-3T3 cells. The first phase was coincident with the increase in Ins(1,4,5)P3 resulting from PtdIns(4,5)P2 hydrolysis, and the second, sustained, phase was derived from phosphatidylcholine (PtdCho) hydrolysis. In NIH-3T3 cells, stimulation by BK induced greater production of choline than phosphocholine in [3H]choline-labelled cells and appreciable phosphatidylethanol (PtdEtOH) formation in [3H]myristic acid-labelled cells, suggesting that PtdCho was hydrolysed mainly by a phospholipase D (PLD) activity. Pretreatment with propranolol, an inhibitor of phosphatidate phosphohydrolase, markedly diminished the second DAG accumulation, supporting the above notion. In DT cells, BK induced predominantly phosphocholine generation and little PtdEtOH formation, indicating that the PtdCho hydrolysis was due to a phospholipase C (PLC) activity. The BK-induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) observed in single DT cells [Fu, Sugimoto, Oki, Murakami, Okano & Nozawa (1991) FEBS Lett. 281, 263-266] were detected as a sustained [Ca2+]i elevation when assayed in a cell suspension. A receptor-operated Ca2+ channel blocker, SK&F 96365, suppressed both the BK-induced phosphocholine generation and the sustained [Ca2+]i elevation in a similar dose-dependent manner. These results thus suggested that oscillations in [Ca2+]i are involved in the activation of PtdCho-specific PLC in DT cells.


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