Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues

Laing, Suzette; Wang, Guohui; Briazova, Tamara; Zhang, Chunbin; Wang, Aixia; Zheng, Ze; Gow, Alexander; Chen, Alex F.; Rajagopalan, Sanjay; Chen, Lung Chi; Sun, Qinghua; Zhang, Kezhong

doi:10.1152/ajpcell.00529.2009

Cited by 189 publications

(166 citation statements)

References 56 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…These findings implicating mitochondrial ROS production as the principal source of asbestos-induced free radicals in our model are in accord with our prior studies that include the following: (1) p0-A549 cells lacking mitochondrial DNA and incapable of mitochondrial ROS production, are protected against asbestosinduced DNA damage, p53 activation, and apoptosis (7,8,22); (2) using highly sensitive reduction-oxidation-sensitive green fluorescent proteins targeted to the mitochondria or cytoplasm to detect ROS production, we have previously reported that the mitochondria are the primary source of ROS generation (42); (3) the mitochondria-regulated (intrinsic) death pathway is the primary pathway mediating AEC apoptosis in vitro (7); and (4) a mitochondria-targeted DNA repair protein (8-oxoguanine DNA glycosylase) or mitochondrial aconitase 2 overexpression each prevent oxidant-induced AEC apoptosis, despite high levels of mitochondrial ROS production (42). Our data with asbestosexposed AECs implicating mitochondrial ROS in triggering ER stress also concur with studies showing that antioxidants, including those targeted to the mitochondria, attenuate oxidative stress-induced ER stress and apoptosis in other cell types (30)(31)(32)(33). Mitochondria-targeted antioxidants protect against oxidantinduced ER stress and intrinsic apoptosis of pancreatic beta cells (31,33).…”

Section: Discussionsupporting

confidence: 80%

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 80%

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

View full text Add to dashboard Cite

show abstract

“…4) Antioxidants, including those targeted to the mitochondria, attenuate oxidative stress-induced endoplasmic reticulum stress and intrinsic apoptosis in AEC as well as other cell types (35)(36)(37). Thus, the levels of oxidative stress-induced AEC mtDNA damage are crucial in triggering a DNA damage response (e.g.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells

Kim

Cheresh

Williams

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Mitochondrial Ogg1 prevents oxidant (H 2 O 2 and asbestos)-induced Aco-2 degradation and apoptosis. Results: Oxidant stress caused preferential AEC mtDNA Ͼ nuclear DNA damage, mt-p53 translocation, and apoptosis; effects were blocked by mt-hOgg1 or Aco-2. Conclusion: mt-hOgg1 and Aco-2 preserve AEC mtDNA, preventing oxidant-induced p53 activation and apoptosis. Significance: mt-hOgg1/Aco-2 effects on mtDNA may be an innovative target for preventing degenerative diseases.

show abstract

“…It is also possible that AECs, in their attempt to regenerate the alveolar epithelium after injury, may inherently be under ER stress and UPR activation in their hyperplastic state secondary to intrinsic factors such as increased metabolic demand, thus perpetuating an ongoing injuryremodeling cycle. Finally, exogenous exposures could contribute to ER stress, including herpesviruses, cigarette smoke, and inhaled particulates, all of which have been shown to induce ER stress in lung epithelium (24,25,32,49).…”

Section: Potential Causes Of Er Stress In Ipfmentioning

confidence: 99%

Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis

Tanjore

Blackwell

Lawson

2012

American Journal of Physiology-Lung Cellular and Molecular Phys

198

186

View full text Add to dashboard Cite

show abstract

Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues

Abstract: Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues.

Cited by 189 publications

References 56 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

Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells

Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis

Contact Info

Product

Resources

About