Post-transcriptional Air Pollution Oxidation to the Cholesterol Biosynthesis Pathway Promotes Pulmonary Stress Phenotypes

Overview

Journal Commun Biol

Specialty Biology

Date 2020 Jul 24

PMID 32699268

Citations 14

Authors

Juan C Gonzalez-Rivera

Kevin C Baldridge

Dongyu S Wang

Kanan Patel

Jamie C L Chuvalo-Abraham

Lea Hildebrandt Ruiz

Lydia M Contreras

Affiliations

Soon will be listed here.

Abstract

The impact of environmentally-induced chemical changes in RNA has been fairly unexplored. Air pollution induces oxidative modifications such as 8-oxo-7,8-dihydroguanine (8-oxoG) in RNAs of lung cells, which could be associated with premature lung dysfunction. We develop a method for 8-oxoG profiling using immunocapturing and RNA sequencing. We find 42 oxidized transcripts in bronchial epithelial BEAS-2B cells exposed to two air pollution mixtures that recreate urban atmospheres. We show that the FDFT1 transcript in the cholesterol biosynthesis pathway is susceptible to air pollution-induced oxidation. This process leads to decreased transcript and protein expression of FDFT1, and reduced cholesterol synthesis in cells exposed to air pollution. Knockdown of FDFT1 replicates alterations seen in air pollution exposure such as transformed cell size and suppressed cytoskeleton organization. Our results argue of a possible novel biomarker and of an unseen mechanism by which air pollution selectively modifies key metabolic-related transcripts facilitating cell phenotypes in bronchial dysfunction.

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References

Holguin F . Oxidative stress in airway diseases. Ann Am Thorac Soc. 2013; 10 Suppl:S150-7. DOI: 10.1513/AnnalsATS.201305-116AW. View

James A, Wenzel S . Clinical relevance of airway remodelling in airway diseases. Eur Respir J. 2007; 30(1):134-55. DOI: 10.1183/09031936.00146905. View

Mannino D, Buist A . Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007; 370(9589):765-73. DOI: 10.1016/S0140-6736(07)61380-4. View

Esposito V, Lucariello A, Savarese L, Cinelli M, Ferraraccio F, Bianco A . Morphology changes in human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM₁.₀) and pollen allergens. Environ Pollut. 2012; 171:162-7. DOI: 10.1016/j.envpol.2012.07.006. View

Nishida K, Brune K, Putcha N, Mandke P, ONeal W, Shade D . Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension. Am J Physiol Lung Cell Mol Physiol. 2017; 313(3):L581-L591. PMC: 5625260. DOI: 10.1152/ajplung.00074.2017. View

Heijink I, de Bruin H, van den Berge M, Bennink L, Brandenburg S, Gosens R . Role of aberrant WNT signalling in the airway epithelial response to cigarette smoke in chronic obstructive pulmonary disease. Thorax. 2013; 68(8):709-16. DOI: 10.1136/thoraxjnl-2012-201667. View

Kuperman D, Huang X, Koth L, Chang G, Dolganov G, Zhu Z . Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med. 2002; 8(8):885-9. DOI: 10.1038/nm734. View

Hackett T, Warner S, Stefanowicz D, Shaheen F, Pechkovsky D, Murray L . Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1. Am J Respir Crit Care Med. 2009; 180(2):122-33. DOI: 10.1164/rccm.200811-1730OC. View

McHale C, Zhang L, Hubbard A, Smith M . Toxicogenomic profiling of chemically exposed humans in risk assessment. Mutat Res. 2010; 705(3):172-83. PMC: 2928857. DOI: 10.1016/j.mrrev.2010.04.001. View

10.

Li W, Hu J, Adebali O, Adar S, Yang Y, Chiou Y . Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene. Proc Natl Acad Sci U S A. 2017; 114(26):6752-6757. PMC: 5495276. DOI: 10.1073/pnas.1706021114. View

11.

Oikawa S . Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging. Environ Health Prev Med. 2011; 10(2):65-71. PMC: 2723656. DOI: 10.1007/BF02897995. View

12.

Hosford M, Muller J, Burrows C . Spermine participates in oxidative damage of guanosine and 8-oxoguanosine leading to deoxyribosylurea formation. J Am Chem Soc. 2004; 126(31):9540-1. DOI: 10.1021/ja047981q. View

13.

Dai D, Gan W, Hayakawa H, Zhu J, Zhang X, Hu G . Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells. Proc Natl Acad Sci U S A. 2018; 115(16):4218-4222. PMC: 5910836. DOI: 10.1073/pnas.1718363115. View

14.

Shan X, Tashiro H, Lin C . The identification and characterization of oxidized RNAs in Alzheimer's disease. J Neurosci. 2003; 23(12):4913-21. PMC: 6741200. View

15.

Wurtmann E, Wolin S . RNA under attack: cellular handling of RNA damage. Crit Rev Biochem Mol Biol. 2008; 44(1):34-49. PMC: 2656420. DOI: 10.1080/10409230802594043. View

16.

Deslee G, Adair-Kirk T, Betsuyaku T, Woods J, Moore C, Gierada D . Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. Am J Respir Cell Mol Biol. 2009; 43(5):576-84. PMC: 2970854. DOI: 10.1165/rcmb.2009-0221OC. View

17.

Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj E . Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001; 60(8):759-67. DOI: 10.1093/jnen/60.8.759. View

18.

Mihailovic M, Chen A, Gonzalez-Rivera J, Contreras L . Defective Ribonucleoproteins, Mistakes in RNA Processing, and Diseases. Biochemistry. 2017; 56(10):1367-1382. DOI: 10.1021/acs.biochem.6b01134. View

19.

Andreoli R, Spatari G, Pigini D, Poli D, Banda I, Goldoni M . Urinary biomarkers of exposure and of oxidative damage in children exposed to low airborne concentrations of benzene. Environ Res. 2015; 142:264-72. DOI: 10.1016/j.envres.2015.07.003. View

20.

Cejvanovic V, Kjaer L, Morup Bergholdt H, Henriksen T, Weimann A, Ellervik C . RNA oxidation and iron levels in patients with diabetes. Free Radic Biol Med. 2018; 129:532-536. DOI: 10.1016/j.freeradbiomed.2018.10.420. View