The death of hemopoietic cells on withdrawal CSF occurs by a mechanism known as apoptosis characterized the early degradation chromatin into oligonucleosome-length fragments. Insulin-like growth factor I plays pivotal role in regulation somatic cell mediator hormone action. Animals with low levels circulating IGF-I are more vulnerable to infections and have diminished immune responses. To analyze possibility regulatory hemopoiesis determine its action, we studied effect this survival...

Murine bone marrow-derived cells, dependent on interleukin 3 (IL-3) for their growth in culture, undergo programmed cell, or apoptosis, upon cytokine withdrawal. Here it is reported that a variety of DNA damaging agents cause more rapid onset apoptosis factor-dependent cell line, BAF3, deprived IL-3. In contrast, when cultured the presence IL-3, other promoting factors, BAF3 cells are highly resistant to X-irradiation and cytotoxic drugs etoposide cisplatin. Overexpression bcl2 gene product...

The amphibian tetradecapeptide, bombesin, and structurally related peptides caused a marked increase in ouabain-sensitive 86Rb+ uptake (a measure of Na+/K+ pump activity) quiescent Swiss 3T3 cells. This effect occurred within seconds after the addition peptide appeared to be mediated by an Na+ entry into bombesin on activity was concentration dependent with half-maximal stimulation occurring at 0.3-0.4 nM. litorin, gastrin-releasing peptide, neuromedin B also stimulated uptake; relative...

In the IL-2-dependent T cell clone CTLL-2, dexamethasone, a synthetic glucocorticoid, induces suicide program characterized by early degradation of chromatin in oligonucleosome-length fragments which precedes loss viability 2 to 4 h. These effects are most likely mediated through interaction with specific glucocorticoid receptor as suggested structure-activity relationship various steroids tested. Incubation nuclei glucocorticoid-untreated cells presence calcium and magnesium ions cleavage...

Abstract Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis multicellular organisms. Cytochrome c central figure in activation apoptotic intrinsic pathway, thereby activating caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3ε (a direct inhibitor Apaf-1) as cytosolic cytochrome target. Here we explore / show ability block 14-3-3ε-mediated Apaf-1 inhibition, unveiling novel function for an...

Abstract We have analyzed the effect mediated by prostaglandin E 2 (PGE ) and different reagents that increase intracellular cAMP on expression of p55 subunit (CD25) interleukin receptors (IL2R), levels CD25‐specific mRNA high affinity IL 2R. In purified T cells, activated either an anti‐CD3 monoclonal antibody or phytohemagglutinin, addition PGE (10 −6 M ), forskolin (5 × 10 −5 cholera toxin (0.2 μg/ml) dibutyryl (dBcAMP) −4 decreased cell surface 2R reducing (40%‐78% inhibition)...

Addition of the mitogenic peptides bombesin and vasopressin to quiescent Swiss 3T3 mouse cells increased cytosolic Ca2+ concentration without any measurable delay. In contrast, there was a significant lag period (16 +/- 1.2 s) before platelet-derived growth factor (PDGF) concentration. This not diminished at high concentrations either porcine or human PDGF. Similar results were obtained in loaded with quin-2 fura-2. The differences effects bombesin, vasopressin, PDGF on movements also...

ICE-like protease activation and DNA fragmentation are preceded by a decrease in intracellular pH (pHi) during apoptosis the IL-3 dependent cell line BAF3. Acidification occurs after 7 hours cells deprived of 4 when treated with etoposide, close to time detection activity. Increasing extracellular reduces fragmentation. Bcl-2 over-expression both delays acidification inhibits activation. Generation rapid decrease, using ionophore nigericin, induces apoptosis. ZVAD, permeable inhibitor...

Tumors display a high rate of glucose uptake and glycolysis. We investigated how inhibition metabolism could affect death receptor-mediated apoptosis in human tumor cells diverse origin. show that both substitution for pyruvate treatment with 2-deoxyglucose enhanced induced by necrosis factor (TNF)-alpha, CD95 agonistic antibody, TNF-related apoptosis-inducing ligand (TRAIL). Inhibition killing myeloid leukemia U937, cervical carcinoma HeLa, breast MCF-7 upon receptor ligation. Caspase...

Abstract The cyclin-dependent kinase inhibitor flavopiridol is undergoing clinical trials as an antitumor drug. We show here that pretreatment of different human breast cancer cell lines with facilitates tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis. In cells, apoptosis induction by TRAIL blocked at the level apical caspase-8 activation. Flavopiridol treatment enhances TRAIL-induced formation death-inducing signaling complex and early processing...

In recent years, several studies have confirmed the clonal elimination of thymocytes with receptors that recognize Ag and MHC molecules present on membrane thymic stromal cells, a process may be relevant to establishment self-tolerance. our work, we show anti-CD3 treatment single positive CD4+ or CD8+ human medullary (obtained by anti-CD1a plus C) induces their apoptotic death. Some events commonly associated early steps normal activation (IL-2R expression, increase in cytoplasmic Ca2+) are...

The stimulation of DNA synthesis in cultures Swiss 3T3 cells by vasopressin, epidermal growth factor, and insulin added serum-free medium is strikingly dependent on the intracellular K+ content or concentration. relationship between these parameters sigmoid; commences only when increases above a certain threshold level (0.56 mumol/mg protein; 90 mM). Addition to K+- depleted reverses block after lag period at least 8 hr. sigmoid dependence generated early G1 phase rather than G1/S boundary....

Treatment of human breast tumor cells with interferon-gamma (IFN-gamma) elevates caspase-8 expression and sensitizes these to death receptor-mediated apoptosis through the increased processing activation apical procaspase-8. We have characterized gene promoter studied transcriptional regulation in MCF-7 treated IFN-gamma. Our findings show that IFN-gamma induces up-regulation mRNA a protein synthesis-dependent mechanism involving action IFN-gamma-inducible transcription factor interferon...

HER2/Neu/ERBB2 is a receptor tyrosine kinase overexpressed in approximately 20% of human breast tumors. Truncated or mutant isoforms that show increased oncogenicity compared with the wild-type are found many Here, we report constitutively active ERBB2 sensitizes epithelial cells to agents induce endoplasmic reticulum stress, altering unfolded protein response (UPR) these cells. Deregulation ERK, AKT, and mTOR activities elicited by was involved mediating this differential UPR response,...

Significance Histone chaperones are key regulators of transcriptional activity in damaged chromatin regions the DNA damage response. Here we show that cytochrome c (C ) targets histone chaperone SET/template-activating factor (TAF)-Iβ (SET/TAF-Iβ) cell nucleus upon damage, resulting blocking SET/TAF-Iβ function. C is actually translocated into nuclei cells treated with specific inducers and not death-receptor pathway or stress-induced stimuli. locks domains engaged binding SET/TAF-Iβ,...

AMPK is a central energy sensor linking extracellular milieu fluctuations with the autophagic machinery. In current study we uncover that Poly(ADP-ribosyl)ation (PARylation), post-translational modification (PTM) of proteins, accounts for spatial and temporal regulation autophagy by modulating subcellular localisation activation. More particularly, show minority pool needs to be exported cytosol in PARylation-dependent manner optimal induction autophagy, including ULK1 phosphorylation mTORC1...

Abstract In tumors, cancer cells are frequently exposed to adverse environmental conditions that result in endoplasmic reticulum (ER) stress. Mechanical signals emerging from extracellular matrix (ECM) rigidity and cell shape regulate the activity of transcriptional co-activators Yes-associated protein (YAP) its paralog Transcriptional Coactivator with PDZ-binding motif (TAZ). However, role ECM YAP/TAZ tumor fate decisions under ER stress remains relatively unexplored. Our results suggest...