DOI QR코드

DOI QR Code

The Impact of Autophagy on the Cigarette Smoke Extract-Induced Apoptosis of Bronchial Epithelial Cells

  • Lee, Chang-Hoon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital) ;
  • Lee, Kyoung-Hee (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital) ;
  • Jang, An-Hee (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital) ;
  • Yoo, Chul-Gyu (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital)
  • Received : 2016.04.15
  • Accepted : 2016.11.04
  • Published : 2017.01.31

Abstract

Background: Previous studies report that apoptosis and autophagy are involved in the pathogenesis of emphysema, and macroautophagy is one of the processes regulating the apoptosis pathway. However, few studies have evaluated whether chaperone-mediated autophagy (CMA) contributes to the regulation of apoptosis. In this study, we investigated the impact of autophagy, including both macroautophagy and CMA, on the apoptosis in bronchial epithelial cells. Methods: Cigarette smoke extract (CSE) was injected intratracheally into C57BL/6 mice, and emphysema and apoptosis were evaluated in the lungs. After treatment with CSE, apoptosis, macroautophagy, and CMA were measured in BEAS2-B cells, and the impact of autophagy on the apoptosis was evaluated following knockdown of autophagy-related genes by short interfering RNAs (siRNAs). Results: Intratracheal CSE injection resulted in the development of emphysema and an increase in apoptosis in mice. CSE increased the apoptosis in BEAS2-B cells, and also elevated the expression of proteins related to both macroautophagy and CMA in BEAS2-B cells. The knockdown experiment with siRNAs showed that macroautophagy increases apoptosis in BEAS2-B cells, while CMA suppresses apoptosis. Conclusion: The intratracheal injection of CSE induces pulmonary emphysema and an increase in apoptosis in mice. CSE also induces apoptosis, macroautophagy, and CMA of bronchial epithelial cells. Macroautophagy and CMA regulate apoptosis in opposite directions.

Acknowledgement

Supported by : Korean Academy of Tuberculosis and Respiratory Diseases

References

  1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, updated 2016. Global Initiative for Chronic Obstructive Lung Disease; 2016.
  2. Decramer M, Janssens W, Miravitlles M. Chronic obstructive pulmonary disease. Lancet 2012;379:1341-51. https://doi.org/10.1016/S0140-6736(11)60968-9
  3. Yoo KH, Kim YS, Sheen SS, Park JH, Hwang YI, Kim SH, et al. Prevalence of chronic obstructive pulmonary disease in Korea: the fourth Korean National Health and Nutrition Examination Survey, 2008. Respirology 2011;16:659-65. https://doi.org/10.1111/j.1440-1843.2011.01951.x
  4. Abboud RT, Vimalanathan S. Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema. Int J Tuberc Lung Dis 2008;12:361-7.
  5. Rahman I. Oxidative stress in pathogenesis of chronic obstructive pulmonary disease: cellular and molecular mechanisms. Cell Biochem Biophys 2005;43:167-88. https://doi.org/10.1385/CBB:43:1:167
  6. O'Donnell R, Breen D, Wilson S, Djukanovic R. Inflammatory cells in the airways in COPD. Thorax 2006;61:448-54. https://doi.org/10.1136/thx.2004.024463
  7. Fischer BM, Pavlisko E, Voynow JA. Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation. Int J Chron Obstruct Pulmon Dis 2011;6:413-21.
  8. Demedts IK, Demoor T, Bracke KR, Joos GF, Brusselle GG. Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. Respir Res 2006;7:53. https://doi.org/10.1186/1465-9921-7-53
  9. Park JW, Ryter SW, Choi AM. Functional significance of apoptosis in chronic obstructive pulmonary disease. COPD 2007;4:347-53. https://doi.org/10.1080/15412550701603775
  10. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell 2011;147:728-41. https://doi.org/10.1016/j.cell.2011.10.026
  11. Kiriyama Y, Nochi H. The function of autophagy in neurodegenerative diseases. Int J Mol Sci 2015;16:26797-812. https://doi.org/10.3390/ijms161125990
  12. Zeki AA, Yeganeh B, Kenyon NJ, Post M, Ghavami S. Autophagy in airway diseases: a new frontier in human asthma? Allergy 2016;71:5-14. https://doi.org/10.1111/all.12761
  13. Araya J, Hara H, Kuwano K. Autophagy in the pathogenesis of pulmonary disease. Intern Med 2013;52:2295-303. https://doi.org/10.2169/internalmedicine.52.1118
  14. Bejarano E, Cuervo AM. Chaperone-mediated autophagy. Proc Am Thorac Soc 2010;7:29-39. https://doi.org/10.1513/pats.200909-102JS
  15. Ryter SW, Lam HC, Chen ZH, Choi AM. Deadly triplex: smoke, autophagy and apoptosis. Autophagy 2011;7:436-7. https://doi.org/10.4161/auto.7.4.14501
  16. Lee KH, Lee CH, Jeong J, Jang AH, Yoo CG. Neutrophil elastase differentially regulates interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) production by cigarette smoke extract. J Biol Chem 2015;290:28438-45. https://doi.org/10.1074/jbc.M115.663567
  17. Wright JL, Cosio M, Churg A. Animal models of chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol 2008;295:L1-15. https://doi.org/10.1152/ajplung.90200.2008
  18. Wu H, Chen S, Ammar AB, Xu J, Wu Q, Pan K, et al. Crosstalk between macroautophagy and chaperone-mediated autophagy: implications for the treatment of neurological diseases. Mol Neurobiol 2015;52:1284-96. https://doi.org/10.1007/s12035-014-8933-0
  19. Koga H, Martinez-Vicente M, Arias E, Kaushik S, Sulzer D, Cuervo AM. Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease. J Neurosci 2011;31:18492-505. https://doi.org/10.1523/JNEUROSCI.3219-11.2011
  20. Kaushik S, Massey AC, Mizushima N, Cuervo AM. Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy. Mol Biol Cell 2008;19:2179-92. https://doi.org/10.1091/mbc.e07-11-1155
  21. Massey AC, Kaushik S, Sovak G, Kiffin R, Cuervo AM. Consequences of the selective blockage of chaperone-mediated autophagy. Proc Natl Acad Sci U S A 2006;103:5805-10. https://doi.org/10.1073/pnas.0507436103
  22. Wang Y, Singh R, Massey AC, Kane SS, Kaushik S, Grant T, et al. Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. J Biol Chem 2008;283:4766-77. https://doi.org/10.1074/jbc.M706666200