The Changes of Autophage-Related Protein in Lung Tissues of COPD Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YuHaiyang , LiYan ,  HanFengfeng , LuoYong , XuWeiguo

Departmant of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China;

Corresponding author：

HanFengfeng, Email: fengfh86@sina.com

Keywords：

Chronic obstructive pulmonary disease; Autophagy; Rats; Lung tissue

DOI：

10.7507/1671-6205.2016110

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the changes of autophage-related protein in lung tissues of rats with chronic obstructive pulmonary disease (COPD). Methods Passive cigarette smoking was used to establish COPD model in rats. The mRNA and protein expressions of PI3K, total AKT, phosphorylated-AKT, total mTOR, phosphorylated-mTOR, and autophagy-related genes including LC3Ⅱ/Ⅰ, Beclin1, Atg5, Atg7, Atg12, P62 in lung tissues were measured by real-time PCR and Western blot. The autophagy level was compared between the COPD rats and the normal rats by LC3B immunohistochemistry. Results Real-time PCR analysis showed that the mRNA expressions of Beclin1, Atg5 and Atg12 significantly increased in lung tissues of the COPD rats compared with the normal rats (all P < 05). There was no significant difference between the COPD rats and the normal rats as for Atg7 mRNA expression (P > 0.05). Western blot analysis showed that the protein expressions of PI3K, p-AKT/AKT and p-mTOR/mTOR significantly decreased, the protein expressions of LC3 Ⅱ/Ⅰ, Atg5, and Beclin1 increased, and protein expression of P62 significantly decreased in lung tissues of the COPD rats compared with the normal rats (all P < 05). LC3B immunohistochemistry showed that the LC3B expression was higher in the COPD rats than that in the normal rats. Conclusion The level of autophagy significantly increases in COPD rats with decreased expression of upstream proteins in autophagy signal pathway and increased expression of autophage proteins.

Citation： Yu Haiyang, Li Yan, Han Fengfeng, Luo Yong, Xu Weiguo. The Changes of Autophage-Related Protein in Lung Tissues of COPD Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(5): 470-476. doi: 10.7507/1671-6205.2016110 Copy

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2. Plant PJ, Brooks D, Faughnan M, et al. Cellular markers of muscle atrophy in chronic obstructive pulmonary disease.Am J Respir Cell Mol Biol, 2010, 42:461-471.
3. Fischer BM, Pavlisko E, Voynow JA, et al. Pathogenic triad in COPD:oxidative stress, protease-antiprotease imbalance, and inflammation.Int J Chron Obstruct Pulmon Dis, 2011, 6:413-421.
4. 李艳丽, 韩锋锋, 李妍, 等.PI3K/AKT/mTOR途径在慢性阻塞性肺疾病大鼠骨骼肌萎缩中的作用.中国呼吸与危重监护杂志, 2014, 13:474-479.
5. 李妍, 韩锋锋, 李艳利, 等.自噬-溶酶体系统在COPD大鼠骨骼肌萎缩中的作用机制.中国呼吸与危重监护杂志, 2015, 14:534-540.
6. Mizushima N, Komatsu M. Autophagy:renovation of cells and tissues. Cell, 2011, 147:728-741.
7. Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell, 2010, 40:280-293.
8. Haspel JA, Choi AM. Autophagy:a core cellular process with emerging links to pulmonary disease.Am J Respir Crit Care Med, 2011, 184:1237-1246.
9. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006, 3:e442.
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11. Chen ZH, Kim HP, Sciurba FC, et al. Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease.PLoS One, 2008, 3:e3316.
12. Kelekar A. Autophagy. Ann NY Acad Sci, 2006, 1066:259-271.
13. Levine B, Yuan J. Autophagy in cell death:an innocent convict? J Clin Invest, 2005, 115:2679-2688.
14. Levine B, Klionsky DJ. Development by self-digestion:molecular mechanisms and biological functions of autophagy. Dev Cell, 2004, 6:463-477.
15. Ryter SW, Chen ZH, Kim HP, et al. Autophagy in chronic obstructive pulmonary disease. Autophagy, 2009, 5:235-237.
16. Klionsky DJ, Abeliovich H, Agostinis P, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher.eukaryotes.Autophagy, 2008, 4:151-175.
17. Yao TP. The role of ubiquitin in autophagy-dependent protein aggregate processing. Genes Cancer, 2011, 1:779-786.
18. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signaling controls tumour cell growth.Nature, 2006, 441:424-430.
19. Saiki S, Sasazawa Y, Imamichi Y, et al. Caffeine induces apoptosis by enhance of autophagy via PI3K/AKT/p70S6K inhibition.Autophagy, 2011, 7:176-187.
20. Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, et al. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegenation. Cell Signal, 2014, 26:2694-2701.
21. Fan S, Zhang B, Luan P, et al. PI3K/AKT/p70S6K pathway is involved in Aβ25-35-induced autophagy.Biomed Res Int, 2015, 2015:161020.
22. Wullschleger S, Loewith R, Hall MN, et al. mTOR signaling in growth and metabolism.Cell, 2006, 124:471-484.
23. Ryter SW, Choi AM. Autophagy in lung disease disease pathogenesis and therapeutics.Redox Biol, 2015, 4:215-225.
24. Hsieh MJ, Tsai TL, Hsieh YS, et al. Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/AKT and JNK signaling pathways in human lung cancer cell lines.Arch Toxicol, 2013, 87:1927-1937.
25. Zi D, Zhou ZW, Yang YJ, et al. Danusertib induces apoptosis, cell cycle arrest, and autophagy but inhibits epithelial to mesenchymal transition involving PI3K/AKT/mTOR signaling pathway in human ovarian cancer cells.Int J Mol Sci, 2015, 16:27228-27251.

Chinese Journal of Respiratory and Critical Care Medicine

The Changes of Autophage-Related Protein in Lung Tissues of COPD Rats

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