Asbestos-induced Pulmonary Fibrosis is Augmented in 8-oxoguanine DNA Glycosylase Knockout Mice

Overview

Journal Am J Respir Cell Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2014 Jun 12

PMID 24918270

Citations 29

Authors

Paul Cheresh

Luisa Morales-Nebreda

Seok-Jo Kim

Anjana Yeldandi

David B Williams

Yuan Cheng

Gokhan M Mutlu

G R Scott Budinger

Karen Ridge

Paul T Schumacker

Vilhelm A Bohr

David W Kamp

Affiliations

Soon will be listed here.

Abstract

Asbestos causes asbestosis and malignancies by mechanisms that are not fully established. Alveolar epithelial cell (AEC) injury and repair are crucial determinants of the fibrogenic potential of noxious agents such as asbestos. We previously showed that mitochondrial reactive oxygen species mediate asbestos-induced AEC intrinsic apoptosis and that mitochondrial human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme, prevents oxidant-induced AEC apoptosis. We reasoned that OGG1 deficiency augments asbestos-induced pulmonary fibrosis. Compared with intratracheal instillation of PBS (50 μl) or titanium dioxide (100 μg/50 μl), crocidolite or Libby amphibole asbestos (100 μg/50 μl) each augmented pulmonary fibrosis in wild-type C57BL/6J (WT) mice after 3 weeks as assessed by histology, fibrosis score, lung collagen via Sircol, and type 1 collagen expression; these effects persisted at 2 months. Compared with WT mice, Ogg1 homozygous knockout (Ogg1(-/-)) mice exhibit increased pulmonary fibrosis after crocidolite exposure and apoptosis in cells at the bronchoalveolar duct junctions as assessed via cleaved caspase-3 immunostaining. AEC involvement was verified by colocalization studies using surfactant protein C. Asbestos increased endoplasmic reticulum stress in the lungs of WT and Ogg1(-/-) mice. Compared with WT, alveolar type 2 cells isolated from Ogg1(-/-) mice have increased mtDNA damage, reduced mitochondrial aconitase expression, and increased P53 and cleaved caspase-9 expression, and these changes were enhanced 3 weeks after crocidolite exposure. These findings suggest an important role for AEC mtDNA integrity maintained by OGG1 in the pathogenesis of pulmonary fibrosis that may represent a novel therapeutic target.

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References

Karahalil B, Hogue B, de Souza-Pinto N, Bohr V . Base excision repair capacity in mitochondria and nuclei: tissue-specific variations. FASEB J. 2002; 16(14):1895-902. DOI: 10.1096/fj.02-0463com. View

Berger F, Vaslin L, Belin L, Asselain B, Forlani S, Humbert S . The impact of single-nucleotide polymorphisms (SNPs) in OGG1 and XPC on the age at onset of Huntington disease. Mutat Res. 2013; 755(2):115-9. DOI: 10.1016/j.mrgentox.2013.04.020. View

Zheng D, Limmon G, Yin L, Leung N, Yu H, Chow V . A cellular pathway involved in Clara cell to alveolar type II cell differentiation after severe lung injury. PLoS One. 2013; 8(8):e71028. PMC: 3734298. DOI: 10.1371/journal.pone.0071028. View

Mossman B, Lippmann M, Hesterberg T, Kelsey K, Barchowsky A, Bonner J . Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos. J Toxicol Environ Health B Crit Rev. 2011; 14(1-4):76-121. PMC: 3118517. DOI: 10.1080/10937404.2011.556047. View

Cardin R, Piciocchi M, Tieppo C, Maddalo G, Zaninotto G, Mescoli C . Oxidative DNA damage in Barrett mucosa: correlation with telomeric dysfunction and p53 mutation. Ann Surg Oncol. 2013; 20 Suppl 3:S583-9. DOI: 10.1245/s10434-013-3043-1. View

Lawson W, Crossno P, Polosukhin V, Roldan J, Cheng D, Lane K . Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Am J Physiol Lung Cell Mol Physiol. 2008; 294(6):L1119-26. DOI: 10.1152/ajplung.00382.2007. View

Panduri V, Weitzman S, Chandel N, Kamp D . Mitochondrial-derived free radicals mediate asbestos-induced alveolar epithelial cell apoptosis. Am J Physiol Lung Cell Mol Physiol. 2004; 286(6):L1220-7. DOI: 10.1152/ajplung.00371.2003. View

Kamp D . Asbestos-induced lung diseases: an update. Transl Res. 2009; 153(4):143-52. PMC: 3544481. DOI: 10.1016/j.trsl.2009.01.004. View

Tsui K, Feng T, Lin Y, Chang P, Juang H . p53 downregulates the gene expression of mitochondrial aconitase in human prostate carcinoma cells. Prostate. 2010; 71(1):62-70. DOI: 10.1002/pros.21222. View

10.

Panduri V, Liu G, Surapureddi S, Kondapalli J, Soberanes S, de Souza-Pinto N . Role of mitochondrial hOGG1 and aconitase in oxidant-induced lung epithelial cell apoptosis. Free Radic Biol Med. 2009; 47(6):750-9. PMC: 4331123. DOI: 10.1016/j.freeradbiomed.2009.06.010. View

11.

Bohr V, Stevnsner T, de Souza-Pinto N . Mitochondrial DNA repair of oxidative damage in mammalian cells. Gene. 2002; 286(1):127-34. DOI: 10.1016/s0378-1119(01)00813-7. View

12.

Nuorva K, Makitaro R, Huhti E, Kamel D, Vahakangas K, Bloigu R . p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke. Am J Respir Crit Care Med. 1994; 150(2):528-33. DOI: 10.1164/ajrccm.150.2.8049841. View

13.

Van Houten B, Woshner V, Santos J . Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair (Amst). 2005; 5(2):145-52. DOI: 10.1016/j.dnarep.2005.03.002. View

14.

Kamp D, Israbian V, Yeldandi A, Panos R, Graceffa P, Weitzman S . Phytic acid, an iron chelator, attenuates pulmonary inflammation and fibrosis in rats after intratracheal instillation of asbestos. Toxicol Pathol. 1995; 23(6):689-95. DOI: 10.1177/019262339502300606. View

15.

Fukae J, Mizuno Y, Hattori N . Mitochondrial dysfunction in Parkinson's disease. Mitochondrion. 2007; 7(1-2):58-62. DOI: 10.1016/j.mito.2006.12.002. View

16.

Noble P, Barkauskas C, Jiang D . Pulmonary fibrosis: patterns and perpetrators. J Clin Invest. 2012; 122(8):2756-62. PMC: 3408732. DOI: 10.1172/JCI60323. View

17.

Husgafvel-Pursiainen K, Kannio A, Oksa P, Suitiala T, Koskinen H, Partanen R . Mutations, tissue accumulations, and serum levels of p53 in patients with occupational cancers from asbestos and silica exposure. Environ Mol Mutagen. 1997; 30(2):224-30. View

18.

Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M . Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008; 178(8):838-46. PMC: 2566794. DOI: 10.1164/rccm.200802-313OC. View

19.

Roepke M, Diestel A, Bajbouj K, Walluscheck D, Schonfeld P, Roessner A . Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol Ther. 2007; 6(2):160-9. DOI: 10.4161/cbt.6.2.3575. View

20.

Gredilla R, Bohr V, Stevnsner T . Mitochondrial DNA repair and association with aging--an update. Exp Gerontol. 2010; 45(7-8):478-88. PMC: 2879476. DOI: 10.1016/j.exger.2010.01.017. View