Asbestos-induced alveolar epithelial cell apoptosis: The role of endoplasmic reticulum stress response

David W. Kamp*, Gang Liu, Paul Cheresh, Seok Jo Kim, Amanda Mueller, Anna P. Lam, Humberto Trejo, David Williams, Sandhya Tulasiram, Margaret Baker, Karen Ridge, Navdeep S. Chandel, Rohinee Beri

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 as bestos fibers increased AEC mRNA and protein expression of E Rstress proteins involvedin the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as wellas ERCa2+ release,as assessedby aFURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-X L in A549 cells eachattenuate asbestos-induced AECERstress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca2+ release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AECapoptosis, and eukarion-134orBcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuatesERstress, blocksasbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca2+ release or apoptosis. These results showthat asbestos triggers an AECER stress response and subsequent intrinsic apoptosis thatismediatedinpart by ER Ca2+ release.

Original languageEnglish (US)
Pages (from-to)892-901
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number6
DOIs
StatePublished - Dec 1 2013

Fingerprint

Alveolar Epithelial Cells
Endoplasmic Reticulum Stress
Asbestos
Apoptosis
Endoplasmic Reticulum
Inositol
Asbestosis
Thapsigargin
Phosphotransferases
Pulmonary Fibrosis
Proteins
Carrier Proteins
Amosite Asbestos
Unfolded Protein Response
Protein Unfolding
Idiopathic Pulmonary Fibrosis
Mesothelioma
Epithelial Cells
Catalase
Protein Kinases

Keywords

  • Alveolar epithelium
  • Apoptosis
  • Asbestos
  • Endoplasmic reticulum
  • Mitochondria

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Kamp, David W. ; Liu, Gang ; Cheresh, Paul ; Kim, Seok Jo ; Mueller, Amanda ; Lam, Anna P. ; Trejo, Humberto ; Williams, David ; Tulasiram, Sandhya ; Baker, Margaret ; Ridge, Karen ; Chandel, Navdeep S. ; Beri, Rohinee. / Asbestos-induced alveolar epithelial cell apoptosis : The role of endoplasmic reticulum stress response. In: American journal of respiratory cell and molecular biology. 2013 ; Vol. 49, No. 6. pp. 892-901.
@article{093a6cb2467f4760b23f3654d6dd2abb,
title = "Asbestos-induced alveolar epithelial cell apoptosis: The role of endoplasmic reticulum stress response",
abstract = "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 as bestos fibers increased AEC mRNA and protein expression of E Rstress proteins involvedin the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as wellas ERCa2+ release,as assessedby aFURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-X L in A549 cells eachattenuate asbestos-induced AECERstress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca2+ release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AECapoptosis, and eukarion-134orBcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuatesERstress, blocksasbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca2+ release or apoptosis. These results showthat asbestos triggers an AECER stress response and subsequent intrinsic apoptosis thatismediatedinpart by ER Ca2+ release.",
keywords = "Alveolar epithelium, Apoptosis, Asbestos, Endoplasmic reticulum, Mitochondria",
author = "Kamp, {David W.} and Gang Liu and Paul Cheresh and Kim, {Seok Jo} and Amanda Mueller and Lam, {Anna P.} and Humberto Trejo and David Williams and Sandhya Tulasiram and Margaret Baker and Karen Ridge and Chandel, {Navdeep S.} and Rohinee Beri",
year = "2013",
month = "12",
day = "1",
doi = "10.1165/rcmb.2013-0053OC",
language = "English (US)",
volume = "49",
pages = "892--901",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "6",

}

Asbestos-induced alveolar epithelial cell apoptosis : The role of endoplasmic reticulum stress response. / Kamp, David W.; Liu, Gang; Cheresh, Paul; Kim, Seok Jo; Mueller, Amanda; Lam, Anna P.; Trejo, Humberto; Williams, David; Tulasiram, Sandhya; Baker, Margaret; Ridge, Karen; Chandel, Navdeep S.; Beri, Rohinee.

In: American journal of respiratory cell and molecular biology, Vol. 49, No. 6, 01.12.2013, p. 892-901.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Asbestos-induced alveolar epithelial cell apoptosis

T2 - The role of endoplasmic reticulum stress response

AU - Kamp, David W.

AU - Liu, Gang

AU - Cheresh, Paul

AU - Kim, Seok Jo

AU - Mueller, Amanda

AU - Lam, Anna P.

AU - Trejo, Humberto

AU - Williams, David

AU - Tulasiram, Sandhya

AU - Baker, Margaret

AU - Ridge, Karen

AU - Chandel, Navdeep S.

AU - Beri, Rohinee

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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 as bestos fibers increased AEC mRNA and protein expression of E Rstress proteins involvedin the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as wellas ERCa2+ release,as assessedby aFURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-X L in A549 cells eachattenuate asbestos-induced AECERstress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca2+ release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AECapoptosis, and eukarion-134orBcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuatesERstress, blocksasbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca2+ release or apoptosis. These results showthat asbestos triggers an AECER stress response and subsequent intrinsic apoptosis thatismediatedinpart by ER Ca2+ release.

AB - 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 as bestos fibers increased AEC mRNA and protein expression of E Rstress proteins involvedin the unfolded protein response, such as inositol-requiring kinase (IRE) 1 and X-box-binding protein-1, as wellas ERCa2+ release,as assessedby aFURA-2 assay. Eukarion-134, a superoxide dismutase/catalase mimetic, as well as overexpression of Bcl-X L in A549 cells eachattenuate asbestos-induced AECERstress (IRE-1 and X-box-binding protein-1 protein expression; ER Ca2+ release) and apoptosis. Thapsigargin, a known ER stress inducer, augments AECapoptosis, and eukarion-134orBcl-XL overexpression are protective. Finally, 4-phenylbutyric acid, a chemical chaperone that attenuatesERstress, blocksasbestos- and thapsigargin-induced AEC IRE-1 protein expression, but does not reduce ER Ca2+ release or apoptosis. These results showthat asbestos triggers an AECER stress response and subsequent intrinsic apoptosis thatismediatedinpart by ER Ca2+ release.

KW - Alveolar epithelium

KW - Apoptosis

KW - Asbestos

KW - Endoplasmic reticulum

KW - Mitochondria

UR - http://www.scopus.com/inward/record.url?scp=84890024018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890024018&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2013-0053OC

DO - 10.1165/rcmb.2013-0053OC

M3 - Article

C2 - 23885834

AN - SCOPUS:84890024018

VL - 49

SP - 892

EP - 901

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 6

ER -