Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D01931 (TiO2)
 11,320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asbestos causes asbestosis and malignancies by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) injury by iron-induced reactive oxygen species (ROS) is one important mechanism. To determine whether asbestos causes apoptosis in AECs, we exposed WI-26 (human type I-like cells), A549 (human type II-like cells), and rat alveolar type II cells to amosite asbestos and assessed apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labeling (TUNEL) staining, nuclear morphology, annexin V staining, DNA nucleosome formation, and caspase 3 activation. In contrast to control medium and TiO2, amosite asbestos and H2O2 each caused AEC apoptosis. A role for iron-catalyzed ROS was suggested by the finding that asbestos-induced AEC apoptosis and caspase 3 activation were each attenuated by either an iron chelator (phytic acid and deferoxamine) or a.OH scavenger (dimethyl-thiourea, salicylate, and sodium benzoate) but not by iron-loaded phytic acid. To determine whether asbestos causes apoptosis in vivo, rats received a single intratracheal instillation of amosite (5 mg) or normal saline solution, and apoptosis in epithelial cells in the bronchoalveolar duct regions was assessed by TUNEL staining. One week after exposure, amosite asbestos caused a 3-fold increase in the percentage of apoptotic cells in the bronchoalveolar duct regions as compared with control (control, 2.1% +/- 0.35%; asbestos, 7.61% +/- 0.15%; n = 3). However, by 4 weeks the number of apoptotic cells was similar to control. We conclude that asbestos-induced pulmonary toxicity may partly be caused by apoptosis in the lung epithelium that is mediated by iron-catalyzed ROS and caspase 3 activation.
 ...
PMID:Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals. 1132 27

The inhibitor of differentiation (Id) family of genes, which encodes negative regulators of basic helix-loop-helix transcription factors, has been implicated in diverse cellular processes such as proliferation, apoptosis, differentiation, and migration. However, the specific role of Id1 in titanium dioxide (TiO2)-induced lung injury has not been investigated. In the present study, we investigated whether TiO2 induces apoptosis in H1299 lung cancer cells and by which pathways. Based on the results of the LDH assay, dual staining with Annexin V-FITC and propidium iodide (PI), and RT-PCR analysis of apoptosis-related gene expression, TiO2 caused a dose- and time-dependent decrease in cell viability and appeared to involve both necrosis and apoptosis. Furthermore, Id1 expression was significantly reduced in TiO2-treated cells compared with control cells. To further investigate the functional role of Id1, cells were transduced with a recombinant adenovirus expressing Id1, and the effects on sensitivity to TiO2 were analyzed. Id1 overexpression led to the enhancement of cellular proliferation and reduced the sensitivity of H1299 cells to TiO2. Our results indicate that Id1 expression attenuates the degree of TiO2-induced cytotoxicity in lung cells.
 ...
PMID:Inhibitor of differentiation 1 (Id1) expression attenuates the degree of TiO2-induced cytotoxicity in H1299 non-small cell lung cancer cells. 1948 31

With the increasing clinical use of titanium dioxide (TiO2 ) nanoparticles, a better understanding of their safety in the blood stream is required. The present study evaluates the toxic effect of commercially available TiO2 nanoparticles (~100 nm) using a battery of cytotoxic, genotoxic, hemolytic and morphological parameters. The cytotoxic effects of TiO2 nanoparticles in human lymphocyte cells were studied with respect to membrane damage, mitochondrial function, metabolic activity and lysosomal membrane stability. Genotoxicity in lymphocyte cells was quantitated using a comet assay. The mode of cell death (apoptosis/necrosis) was evaluated using PI/Annexin V staining. TiO2 nanoparticles were also evaluated for their hemolytic properties, osmotic fragility and interaction with hemoglobin. Human erythrocyte cells were studied for morphological alterations using atomic force microscopy (AFM). Results suggest that the particles could induce a significant reduction in mitochondrial dehydrogenase activity in human lymphocyte cells. Membrane integrity remained unaffected by nanoparticle treatment. DNA damage and apoptosis were induced by TiO2 nanoparticles in a dose-dependent manner. A study on human erythrocyte cells revealed a hemolytic property of TiO2 nanoparticles characterized by spherocytosis and echinocytosis. Spectral analysis revealed a hemoglobin TiO2 nanoparticle interaction. Our in vitro study results suggest that commercially available blood contacting nanoparticles (TiO2 nanoparticle) should be carefully evaluated for their toxic potential.
 ...
PMID:Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2 ) nanoparticles on human erythrocyte and lymphocyte cells in vitro. 2361 99

In this study, folic acid surface modified-Titanium dioxide nanoparticles (FA-TiNP) were prepared as a suitable alternative to conventional chemotherapeutic agents to treat human osteosarcoma. The particle size of TiNP increased marked after polymer assembly on the nanoparticles (NP) surface with a spherical morphology. FA-TiNP exhibited a superior anticancer effect in osteosarcoma cancer cells compared to that of bare TiNP. The reason might due to the specific interaction of FA with the folate receptor which is overexpressed in the cancer cells. Especially, FA-TiNP treated cells exhibited chromatin condensation, cell shrinkage and membrane blebbing. FA-TiNP showed significantly higher cancer cell apoptosis with nearly 38% of cells in apoptosis chamber (early and late) compared to only ~16% for TiNP. The higher proportion of Annexin V positive cells for FA-TiNP treated group was mainly attributed to the higher intracellular uptake of the TiO2. Importantly, FA-TiNP increased the sub-G0 population to ~25% indicating its superior anticancer effect. The results clearly indicated that FA-TiNP induced greater reactive oxygen species (ROS) generation that resulted in higher sub-G0 cell population with higher cell apoptosis. FA-TiNP showed a remarkably higher expression of cytochrome C (Cyt C) with a marked increase in the expression of cleaved caspase-3 and PARP. Overall, results suggest that surface modification of TiNP with a specific targeting moiety could enhance the chances of having successful therapies for cancer diseases.
 ...
PMID:Folic acid-tagged titanium dioxide nanoparticles for enhanced anticancer effect in osteosarcoma cells. 2848 84