Nerve growth factor and brain-derived neurotrophic factor but not granulocyte colony-stimulating factor, nimodipine and dizocilpine, require ATP for neuroprotective activity after oxygen–glucose deprivation of primary neurons

2012 ◽  
Vol 1448 ◽  
pp. 20-26 ◽  
Author(s):  
Katja B. Ferenz ◽  
Ronald E. Gast ◽  
Karsten Rose ◽  
Indra E. Finger ◽  
Anja Hasche ◽  
...  
Author(s):  
Ning Xie ◽  
Qin Huang ◽  
Jingting Han ◽  
Wenyuan Xu

IntroductionThis study aims to determine the relationship between the granulocyte colony-stimulating factor (G-CSF) and the Notch signaling pathway in ischemic brain injury.Material and methodsPC-12 cells were treated with the nerve growth factor (NGF) to induce neuronal differentiation then divided into seven groups: 1) no treatment (control); 2) oxygen-glucose deprivation (OGD) model; 3) overexpressed G-CSF + OGD model; 4) transfected empty vector (negative control; NC) + OGD model; 5) overexpressed G-CSF + γ-secretase inhibitor MW167 + OGD model; 6) MW167 + OGD model; and 7) NC + MW167 + OGD model. The cells were analyzed using immunohistochemistry and apoptosis and CCK8 assays. The expression of the related molecules in the Notch pathway was detected using the Western blotting and quantitative PCR (Q-PCR).ResultsMost PC-12 cells were neuron-specific enolase (NSE)-positive after the NGF treatment. When compared with the control group, the MW167 + OGD and NC + MW167 + OGD groups had the lowest optical density (OD) values, followed by the OGD, NC + OGD and the G-CSF + MW167+ OGD groups. The G-CSF + OGD group had the highest OD value. Concerning apoptosis detection, the control group had the lowest apoptosis rate. The highest apoptosis rates were found in the MW167 + OGD, the OGD, and then the G-CSF + OGD groups.ConclusionsThe blocking of the Notch pathway can attenuate the G-CSF effects, whereas the G-CSF overexpression can activate the Notch pathway to resist the effects of oxygen-glucose deprivation.


Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4996-5001 ◽  
Author(s):  
Arnold Freedman ◽  
Donna Neuberg ◽  
Peter Mauch ◽  
John Gribben ◽  
Robert Soiffer ◽  
...  

Abstract Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF ]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.


Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1951-1959 ◽  
Author(s):  
AR Migliaccio ◽  
G Migliaccio ◽  
DC Dale ◽  
WP Hammond

Abstract The number and growth factor requirements of committed progenitor cells (colony-forming units-granulocyte/macrophage and burst-forming units- erythroid) in three patients with cyclic neutropenia (two congenital, one acquired) were studied before and during therapy with recombinant human granulocyte colony-stimulating factor (G-CSF; 3 to 10 micrograms/kg/d). When the patients with congenital disease were treated with G-CSF, the cycling of blood cells persisted, but the cycle length was shortened from 21 days to 14 days, and the amplitude of variations in blood counts increased. There was a parallel shortening of the cycle and increase of the amplitude of variations (from two- to three-fold to 10- to 100-fold) in the number of both types of circulating progenitor cells in these two patients. In the patient with acquired cyclic neutropenia, cycling of both blood cells and progenitors could not be seen. In cultures deprived of fetal bovine serum, erythroid and myeloid bone marrow progenitor cells from untreated patients and from normals differed in growth factor responsiveness. As examples, maximal growth of granulocyte/macrophage (GM) colonies was induced by granulocyte/macrophage (GM)-CSF plus G-CSF in the patients, whereas a combination of GM-CSF, G-CSF and interleukin- 3 (IL-3) was required in the normals, and erythropoietin alone induced fourfold more erythroid bursts from cyclic neutropenic patients than from normal donors (46% versus 11% of the maximal colony number, respectively). The growth factor responsiveness of marrow progenitor cells slightly changed during the treatment toward the values observed with normal progenitors. These results indicate that treatment with G- CSF not only ameliorated the neutropenia, but also increased the amplitude and the frequency of oscillation of circulating progenitor cell numbers. These data are consistent with the hypothesis that G-CSF therapy affects the proliferation of the hematopoietic stem cell.


Stem Cells ◽  
2017 ◽  
Vol 36 (2) ◽  
pp. 252-264 ◽  
Author(s):  
Sadhna O. Piryani ◽  
Angel Y. F. Kam ◽  
Evelyna G. Kliassov ◽  
Benny J. Chen ◽  
Neil L. Spector ◽  
...  

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 971-979 ◽  
Author(s):  
T Tsuda ◽  
D Wong ◽  
J Dolovich ◽  
J Bienenstock ◽  
J Marshall ◽  
...  

Abstract We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose- dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo- CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.


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