X Radiation Causes a Persistent Induction of Reactive Oxygen Species and a Delayed Reinduction of TP53 in Normal Human Diploid Fibroblasts

2002 ◽  
Vol 158 (2) ◽  
pp. 210-219 ◽  
Author(s):  
R. E. Rugo ◽  
M. B. Secretan ◽  
R. H. Schiestl
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Normal Human

Stimulatory Auto-Antibodies to the PDGF Receptor in Patients with Chronic GVHD.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 454-454
Author(s):  
Attilio Olivieri ◽  
Silvia Svegliati ◽  
Nadia Campelli ◽  
Michele Maria Luchetti ◽  
Silvia Trappolini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Type I Collagen ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Type I ◽  
Collagen Gene ◽  
Pdgf Receptor ◽  
Oxygen Species ◽  
Normal Human

Abstract Background Experimental data are consistent with the hypothesis that activation of the PDGF receptor (PDGFR) is characteristic of scleroderma (SSc) fibroblasts and may contribute to their activation. We have recently demonstrated that fibroblasts from SSc patients contain high Ha Ras and ROS (Reactive Oxygen Species) levels and constitutive activation of ERK1/2 (Svegliati et al: JBC in press). Furthermore, SSc patients have circulating auto-antibodies against the PDGFR which induce type I collagen gene expression in normal human fibroblasts through the Ha Ras-ERK1/2- ROS pathway (Svegliati et al: Submitted). These findings suggest that anti PDGFR auto-antibodies play a pivotal role in the pathogenesis of scleroderma. Clinical chronic graft-versus-host disease (cGVHD) can show manifestations that are very similar to those of SSc. Although it is conceivable that the two diseases can share a similar pathophysiological mechanism there are no data supporting this assumption. In view of these considerations we tested the hypothesis that patients with cGVHD have serum auto-antibodies that stimulate PDGFR and activate collagen gene expression in fibroblasts. Methods Serum from 7 patients with extensive cGVHD showing scleroderma-like features either in the skin or in the lung was analyzed for the presence of stimulatory autoantibodies to PDGFR. Patients receiving allogeneic transplantation, but without any signs of cGVHD were used as controls. The median F-U after transplant was 23 months (range 16–36) in patients with cGVH and 42 (range 9–51) in the control group. The assay was carried by incubating purified IgG of the patients with mouse embryo fibroblasts carrying inactive copies of PDGFR α or β chains (PDGFR −/−) or the same cells expressing PDGFR α or β, respectively. Production of reactive oxygen species was assayed in the presence or absence of specific PDGFR inhibitors. The antibodies were characterized by immunoprecipitation, immunoblotting and absorption experiments in primary human fibroblasts and endothelial cells. Result Stimulatory antibodies to the PDGFR were selectively found in all patients with cGVHD and fibrotic lesions. The antibodies specifically recognized PDGFR, induced tyrosine phosphorylation and ROS accumulation. Their activity was completely and selectively abolished by pre-incubation with cells expressing PDGFR α or β chains or by PDGF receptor tyrosine kinase inhibitor. Anti-PDGFR antibodies induced selectively Ha-Ras-ERK1/2 and ROS cascade and stimulated the expression of type I collagen gene and myofibroblast phenotype conversion in normal human primary fibroblasts. Antibodies were absent in all controls. Conclusions Stimulatory auto-antibodies against PDGFR represent a specific hallmark of patients with cGVHD. Their biological activity on fibroblasts strongly argues for a causal role in the pathogenesis of the disease.

Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

2009 ◽  
Vol 297 (3) ◽  
pp. C632-C644 ◽  
Author(s):  
Jun Jun Zhang ◽  
Min Wu ◽  
Norberta W. Schoene ◽  
Wen-Hsing Cheng ◽  
Thomas T. Y. Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Growth ◽  
Reactive Oxygen ◽  
Human Prostate ◽  
Oxygen Species ◽  
Zinc Status ◽  
Normal Human ◽  
Cellular Zinc ◽  
In Cells

To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with resveratrol (0, 0.5, 1, 2.5, 5, and 10 μM) and zinc [0, 4, 16, and 32 μM, representing zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), and zinc-supplemented (ZS) conditions, respectively]. A progressive reduction in cell growth was observed in cells treated with increasing amounts of resveratrol (2.5–10 μM). Resveratrol at 5 and 10 μM resulted in a dramatic increase in cellular total zinc concentration, especially in ZS cells. Flow cytometry indicated that 10 μM resveratrol induced arrest of the cell cycle at the G2/M phase in association with the observed cell growth inhibition. Data from an in vitro experiment using zinquin as an indicator of intracellular free Zn(II) status demonstrated complex interactions between resveratrol and Zn(II). Fluorescence spectrofluorometry and fluorescence microscopic analyses revealed that intracellular free labile zinc was progressively elevated from nearly twofold in ZS cells with no resveratrol to multifold in ZA and ZS cells with 10 μM resveratrol compared with the corresponding ZN cells. Furthermore, increases in cellular zinc status were associated with elevated levels of reactive oxygen species and senescence, as evidenced by morphological and histochemical changes in cells treated with 2.5 or 10 μM resveratrol, especially in ZA and ZS cells. Taken together, the interaction between resveratrol and zinc in NHPrE cells increases total cellular zinc and intracellular free labile zinc status and, subsequently, reactive oxygen species production and senescence.

scholarly journals A host-pathogen interaction screen identifiesada2as a mediator ofCandida glabratadefences against reactive oxygen species

2018 ◽  
Author(s):  
Ilias Kounatidis ◽  
Lauren Ames ◽  
Rupal Mistry ◽  
Hsueh-lui Ho ◽  
Ken Haynes ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ex Vivo ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Invasive Infections ◽  
Life Threatening ◽  
Normal Human ◽  
New Treatments ◽  
Immune Defences

AbstractCandida glabrata (C. glabrata) forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals.C. glabratadisplays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified fiveC. glabratadeletion mutants (Δada2, Δbas1, Δhir3,Δino2andΔmet31) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response inDrosophilalarvae. This highlighted the importance of these transcription factors inC. glabratainfectivity. Furtherex vivoinvestigation into these mutants revealed the requirement ofC. glabrata ADA2for oxidative stress tolerance. We confirmed this observationin vivowhereby growth of theC. glabrata Δada2strain was permitted only in flies with suppressed production of reactive oxygen species (ROS). Conversely, overexpression ofADA2promotedC. glabratareplication in infected wild type larvae resulting in larval killing. We propose thatADA2orchestrates the response ofC. glabrataagainst ROS-mediated immune defences during infection. With the need to find alternative antifungal treatment forC. glabratainfections, genes required for survival in the host environment, such asADA2, provide promising potential targets.

scholarly journals Increased effectiveness of carbon ions in the production of reactive oxygen species in normal human fibroblasts

2014 ◽  
Vol 56 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Till Dettmering ◽  
Sebastian Zahnreich ◽  
Miriam Colindres-Rojas ◽  
Marco Durante ◽  
Gisela Taucher-Scholz ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Carbon Ions ◽  
Normal Human
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