Beryllium-stimulated reactive oxygen species and macrophage apoptosis
Department of Pharmaceutical Sciences, University of Colorado, Denver, Colorado, United States Free Radical Biology and Medicine
(Impact Factor: 5.74).
05/2005; 38(7):928-37. DOI: 10.1016/j.freeradbiomed.2004.12.014
Beryllium (Be), the etiologic agent of chronic beryllium disease, is a toxic metal that induces apoptosis in human alveolar macrophages. We tested the hypothesis that Be stimulates the formation of reactive oxygen species (ROS) which plays a role in Be-induced macrophage apoptosis. Mouse macrophages were exposed to 100 microM BeSO4 in the absence and presence of the catalytic antioxidant MnTBAP (100 microM). Apoptosis was measured as the percentage of TUNEL+ and caspase-8+ cells. ROS production was measured by flow cytometry using the fluorescence probes, dihydroethidine (DHE) and dichlorofluorescein diacetate (DCFH-DA). Be-exposed macrophages had increased TUNEL+ cells (15+/-1% versus controls 1+/-0.2%, P<0.05) and increased caspase-8+ cells (18.7+/-2% versus controls 1.8+/-0.4%, P<0.05). Be-induced caspase-8 activation, and a 4-fold increase in ROS formation, was ameliorated by exposure to MnTBAP. Hydrogen peroxide (30 microM) exposure potentiated Be-induced caspase-8 activation, and was also attenuated by MnTBAP. Our data are the first to demonstrate that Be stimulates macrophage ROS formation which plays an important role in Be-induced macrophage apoptosis.
Available from: Dongwon Lee
- "We then investigated anti-apoptotic activities of PVAX nanoparticles in H2O2-stimulated cells (Fig. 2g). H2O2-stimulation activated the apoptotic cascade in cells, as evidenced in rightward shift in FITC-Annexin V fluorescence by flow cytometry, in good agreement with the literature1617. In contrast, PVAX nanoparticles exerted inhibitory effects on H2O2-induced apoptosis in a dose-dependent manner. A dose of 100 μg of PVAX nanoparticles significantly (~71%) inhibited H2O2-induced apoptosis. "
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ABSTRACT: The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the most abundant form of ROS produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. Here, we report H2O2-responsive antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA) (PVAX) as a novel I/R-targeted nanotherapeutic agent. PVAX was designed to incorporate VA and H2O2-responsive peroxalate ester linkages covalently in its backbone. PVAX nanoparticles therefore degrade and release VA, which is able to reduce the generation of ROS, and exert anti-inflammatory and anti-apoptotic activity. In hind-limb I/R and liver I/R models in mice, PVAX nanoparticles specifically reacted with overproduced H2O2 and exerted highly potent anti-inflammatory and anti-apoptotic activities that reduced cellular damages. Therefore, PVAX nanoparticles have tremendous potential as nanotherapeutic agents for I/R injury and H2O2-associated diseases.
Available from: PubMed Central
- "Therefore, it is impossible to check directly whetherthere is a possibility that short-term exposure can cause apoptosis. However, the increase of lymphocyte is associated with an increase of inflammatory response, and it may be explained as a result of the inflammatory response and the accompanying oxidative stress by exposure to beryllium (26). Eventually, inflammatory response associated with an increase in macrophage apoptosis, the probability is deemed sufficient. "
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ABSTRACT: To investigate the effects of short-term exposure of beryllium on the human immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95, and NK cells, andthe proportion of B cells and TNFα level in peripheral blood and immunoglobulins in the serum of 43 exposed workers and 34 healthy control subjects were studied. External exposure to beryllium was measured by atomic absorption spectrometer as recommended by the NIOSH analytical method 7300. T lymphocyte subpopulation analysis was carried out with flow cytometer. The working duration of exposed workers was less than 3 months and the mean ambient beryllium level was 3.4 μg/m(3), 112.3 μg/m(3), and 2.3 μg/m(3) in molding (furnace), deforming (grinding), and sorting processes, respectively (cited from Kim et al., 2008). However, ambient beryllium level after process change was non-detectable (< 0.1 μg/m(3)). The number of T lymphocytes and the amount of immunoglobulins in the beryllium-exposed workers and control subjects were not significantly different, except for the total number of lymphocytes and CD95 (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed individuals than in the healthy control subjects. Multiple logistic regression analysis showed lymphocytes to be affected by beryllium exposure (odd ratio = 7.293; p < 0.001). These results show that short-term exposure to beryllium does not induce immune dysfunction but is probably associated with lymphocytes proliferation.
Available from: Young-Ok Son
- "Be is believed to stimulate the formation of ROS, leading to Beinduced macrophage apoptosis . While the molecular mechanisms of Be-induced toxicity have yet to be elucidated, macrophage apoptosis is thought to contribute to the metalinduced CBD  . Be is also suspected to induce oxidative stress through the depletion of endogenous thiol antioxidants and the subsequent increase in ROS generation . "
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ABSTRACT: Occupational and environmental exposures to metals are closely associated with an increased risk of various cancers. Although carcinogenesis caused by metals has been intensively investigated, the exact mechanisms of action are still unclear. Accumulating evidence indicates that reactive oxygen species (ROS) generated by metals play important roles in the etiology of degenerative and chronic diseases. This review covers recent advances in (1) metal-induced generation of ROS and the related mechanisms; (2) the relationship between metal-mediated ROS generation and carcinogenesis; and (3) the signaling proteins involved in metal-induced carcinogenesis, especially intracellular reduction-oxidation-sensitive molecules.
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