Calcium chelatro Quin-2 prevens crocidolite-induced DNA strand breakage in human white blood cells

Faux, Stephen P.; Michelangeli, Francesco; Levy, Leonard S.

doi:10.1016/0027-5107(94)90178-3

Cited by 18 publications

(13 citation statements)

References 26 publications

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“…These findings of oxidative stress-induced ER stress in AECs parallel our earlier studies showing that asbestos fibers and H 2 O 2 induce comparable levels of mitochondrial dysfunction, p53 activation, and intrinsic apoptosis in A549 and rat AT2 cells (7,8,22). Our observation that asbestos activates an ER stress response in AECs concurs with prior in vitro studies showing that asbestos stimulates ER stress in breast cancer and white blood cells (26,41), as well as a rat model of asbestosis demonstrating abnormalities in the ER of AECs (15). Although we chose to focus on AEC ER stress pathway involving IRE-1 expression and ER Ca 21 release given their implicated roles in apoptosis, it will be of interest determining whether other arms of the ER stress pathway contribute to AEC apoptosis after asbestos exposure (e.g.…”

Section: Discussionsupporting

confidence: 91%

“…However, ER Ca 21 release to the mitochondria appears necessary, but not sufficient, for inducing intrinsic apoptosis in some cells (19,24,25). Crocidolite asbestos-induced release of intracellular Ca 21 stores is important in mediating DNA damage in human white blood cells (26). We reasoned that oxidative stress (e.g., asbestos fibers and H 2 O 2 ) augments AEC ER Ca 21 release, which may lead to intrinsic apoptosis.…”

Section: Asbestos Stimulates Aec Er Ca 21 Release and Apoptosismentioning

confidence: 98%

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Asbestos-Induced Alveolar Epithelial Cell Apoptosis. The Role of Endoplasmic Reticulum Stress Response

Kamp

Liu

Cheresh

et al. 2013

Am J Respir Cell Mol Biol

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Asbestos exposure results in pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) apoptosis is important in the development of pulmonary fibrosis after exposure to an array of toxins, including asbestos. An endoplasmic reticulum (ER) stress response and mitochondriaregulated (intrinsic) apoptosis occur in AECs of patients with idiopathic pulmonary fibrosis, a disease with similarities to asbestosis. Asbestos induces AEC intrinsic apoptosis, but the role of the ER is unclear. The objective of this study was to determine whether asbestos causes an AEC ER stress response that promotes apoptosis. Using human A549 and rat primary isolated alveolar type II cells, amosite asbestos fibers increased AEC mRNA and protein expression of ER stress proteins involved in the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein- Asbestos fibers are a naturally occurring group of mineral silicates (amphiboles and chrysotile) in which environmental and occupational exposure causes pulmonary and pleural fibrosis, lung cancer, and mesothelioma by mechanisms that are not fully established (see Refs. 1-3 for review). Alveolar epithelial cell (AEC) apoptosis is one important early event implicated in the pathogenesis of pulmonary fibrosis after exposure to various toxins, including asbestos (3, 4). Asbestos fibers are internalized by AECs soon after exposure, resulting in the production of iron-derived reactive oxygen species (ROS), DNA damage, and apoptosis (1-3). The mitochondria (intrinsic) apoptotic death pathway is mediated by proapoptotic Bcl-2 family members (e.g., Bax, Bak, and others) after activation by diverse stimuli, such as ROS, DNA damage, ceramide, and calcium, while antiapoptotic Bcl-2 family members (e.g., Bcl-2, Bcl-X L , etc.) are protective (5, 6). Apoptotic stimuli subsequently result in permeabilization of the outer mitochondrial membrane, reductions in mitochondrial membrane potential and apoptosome formation that activates caspase-9 and downstream caspase-3. We previously showed that ironderived ROS from the mitochondria mediate asbestos-induced AEC DNA damage and apoptosis via the mitochondria-regulated death pathway, and that overexpression of Bcl-X L is protective (7,8). Endoplasmic reticulum (ER) stress can also lead to intrinsic apoptosis, but its role after asbestos exposure has not been studied. The ER is responsible for both intracellular Ca 21 storage and for the folding, maturation, and transport of nascent proteins. Conditions that disrupt these processes, including oxidative stress, perturbation of Ca 21 , and/or accumulation of unfolded and/or misfolded proteins, result in ER stress (see Refs. 3, 4, 6 for review).Accumulating evidence convincingly show that ER stress occurs in AECs undergoing apoptosis in patients with idiopathic pulmonary fibrosis (IPF), and may contribute to epithelialmesenchymal transition, but the pathophysiologic signific...

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Section: Discussionsupporting

confidence: 91%

Section: Asbestos Stimulates Aec Er Ca 21 Release and Apoptosismentioning

confidence: 98%

Asbestos-Induced Alveolar Epithelial Cell Apoptosis. The Role of Endoplasmic Reticulum Stress Response

Kamp

Liu

Cheresh

et al. 2013

Am J Respir Cell Mol Biol

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“…Iron plays a role in the formation of DNA damage but does not totally account for DNA breakage. DNA strand breaks were also detected in mouse CH31OT1/2 cells treated with crocidolite (55) and human blood cells treated with crocidolite (43).…”

Section: Introductionmentioning

confidence: 90%

Mechanisms of fiber-induced genotoxicity.

Jaurand

1997

Environ Health Perspect

117

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The mechanisms of particle-induced genotoxicity have been investigated mainly with asbestos fibers. The results are summarized and discussed in this paper. DNA damage can be produced by oxidoreduction processes generated by fibers. The extent of damage yield depends on experimental conditions: if iron is present, either on fibers or in the medium, damage is increased. However, iron reactivity does not explain all the results obtained in cell-free systems, as breakage of plasmid DNA was not directly associated with the amount of iron released by the fibers. The proximity of DNA to the site of generation of reactive oxygen species (ROS) is important because these species have an extremely short half-life. Damage to cellular DNA can be produced by oxidoreduction processes that originate from cells during phagocytosis. Secondary molecules that are more stable than ROS are probably involved in DNA damage. Oxidoreduction reactions originating from cells can induce mutations. Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption. In some of these processes, the particle state and fiber dimensions are considered important parameters in the generation of genotoxic effects.

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“…In addition to size and fiber durability being important in fiber pathogenicity, asbestos fibers can generate reactive oxygen species (ROS) from redox reactions catalyzed on the fiber surface or from incomplete phagocytosis of the fibers. ROS can react with DNA, which can cause DNA strand breaks (3,4) and base modifications (5,6) as well as induce cellular oxidative stress in which antioxidant defenses are compromised. Recent studies by Heintz et al (7) have shown that both crocidolite and chrysotile asbestos cause dose dependent and persistent increases in expression of cfos and c-jun in rat pleural mesothelial cells and c-jun in hamster tracheal epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E.

Faux

Howden

1997

Environ Health Perspect

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Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-icB) and activator protein-i (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-KB and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-KB to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NFicB DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-KB DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-icB to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events leading to NF-KB transcription factor induction by asbestos.

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Calcium chelatro Quin-2 prevens crocidolite-induced DNA strand breakage in human white blood cells

Cited by 18 publications

References 26 publications

Asbestos-Induced Alveolar Epithelial Cell Apoptosis. The Role of Endoplasmic Reticulum Stress Response

Asbestos-Induced Alveolar Epithelial Cell Apoptosis. The Role of Endoplasmic Reticulum Stress Response

Mechanisms of fiber-induced genotoxicity.

Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E.

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