Adiponectin ameliorates the apoptotic effects of paraquat on alveolar type Ⅱ cells via improvements in mitochondrial function

He,Yarong; Zou,Liqun; Zhou,Yaxiong; Hu,Hai; Yao,Rong; Jiang,Yaowen; Lau,Wayne  Bond; Yuan,Tun; Huang,Wen; Zeng,Zhi; Cao,Yu

doi:10.3892/mmr.2016.5328

Adiponectin ameliorates the apoptotic effects of paraquat on alveolar type Ⅱ cells via improvements in mitochondrial function

Authors:
- Yarong He
- Liqun Zou
- Yaxiong Zhou
- Hai Hu
- Rong Yao
- Yaowen Jiang
- Wayne Bond Lau
- Tun Yuan
- Wen Huang
- Zhi Zeng
- Yu Cao
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Affiliations: Emergency Medicine Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Emergency Medicine Department, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, P.R. China, Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: May 23, 2016 https://doi.org/10.3892/mmr.2016.5328
Pages: 746-752
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have demonstrated that excessive reactive oxygen/nitrogen species (ROS/RNS)‑induced apoptosis is an important feature of the injury to the lung epithelium in paraquat (PQ) poisoning. However the precise mechanisms of PQ‑induced dysfunction of the mitochondria, where ROS/RNS are predominantly produced, remain to be fully elucidated. Whether globular adiponectin (gAd), a potent molecule protective to mitochondria, regulates the mitochondrial function of alveolar type II cells to reduce PQ‑induced ROS/RNS production remains to be investigated. The current study aimed to investigate the precise mechanisms of PQ poisoning in the mitochondria of alveolar type II cells, and to elucidate the role of gAd in protecting against PQ‑induced lung epithelium injury. Therefore, lung epithelial injury was induced by PQ co‑culture of alveolar type II A549 cells for 24 h. gAd was administrated to and removed from the injured cells in after 24 h. PQ was observed to reduce cell viability and increase apoptosis by ~1.5 fold in A549 cells. The oxidative/nitrative stress, resulting from ROS/RNS and disordered mitochondrial function were evidenced by increased O2‑., NO production and reduced mitochondrial membrane potential (ΔΨ), adenosine 5'‑triphosphate (ATP) content in PQ‑poisoned A549 cells. gAd treatment significantly reversed the PQ‑induced cell injury and mitochondrial dysfunction in A549 cells. The protective effects of gAd were partly abrogated by an adenosine 5'‑monophosphate‑activated protein kinase (AMPK) inhibitor, compound C. The results suggest that reduced ΔΨ and ATP content may result in PQ‑induced mitochondrial dysfunction of the lung epithelium, which constitutes a novel mechanism for gAd exerting pulmonary protection against PQ poisoning via AMPK activation.

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1	Vieira DN and de Azevedo-Bernarda R: Paraquat poisoning. Pulmonary lesions. J Toxicol Clin Exp. 9:177–186. 1989.In French. PubMed/NCBI
2	Cai Q, Lu Z, Hong G, Jiang X, Wu Z, Zheng J, Song Q and Chang Z: Recombinant adenovirus Ad-RUNrf2 reduces paraquat-induced A549 injury. Hum Exp Toxicol. 31:1102–1112. 2012. View Article : Google Scholar : PubMed/NCBI
3	Golbidi S, Botta A, Gottfred S, Nusrat A, Laher I and Ghosh S: Glutathione administration reduces mitochondrial damage and shifts cell death from necrosis to apoptosis in ageing diabetic mice hearts during exercise. Br J Pharmacol. 171:5345–5360. 2014. View Article : Google Scholar : PubMed/NCBI
4	Haagsman HP, Schuurmans EA, Batenburg JJ and Van Golde LM: Phospholipid synthesis in isolated alveolar type II cells exposed in vitro to paraquat and hyperoxia. Biochem J. 245:119–126. 1987. View Article : Google Scholar : PubMed/NCBI
5	Kurokawa H, Sugiyama S, Nozaki T, Sugamura K, Toyama K, Matsubara J, Fujisue K, Ohba K, Maeda H, Konishi M, et al: Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway. Atherosclerosis. 239:375–385. 2015. View Article : Google Scholar : PubMed/NCBI
6	Barreto-Torres G, Hernandez JS, Jang S, Rodríguez-Muñoz AR, Torres-Ramos CA, Basnakian AG and Javadov S: The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPARα-cyclophilin D interaction in cardiomyocytes. Am J Physiol Heart Circ Physiol. 308:H749–H758. 2015. View Article : Google Scholar : PubMed/NCBI
7	Berg AH, Combs TP and Scherer PE: ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab. 13:84–89. 2002. View Article : Google Scholar : PubMed/NCBI
8	Okamoto Y, Kihara S, Funahashi T, Matsuzawa Y and Libby P: Adiponectin: A key adipocytokine in metabolic syndrome. Clin Sci (Lond). 110:267–278. 2006. View Article : Google Scholar
9	Robinson K, Prins J and Venkatesh B: Clinical review: Adiponectin biology and its role in inflammation and critical illness. Crit Care. 15:2212011. View Article : Google Scholar : PubMed/NCBI
10	Kadowaki T, Yamauchi T and Kubota N: The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett. 582:74–80. 2008. View Article : Google Scholar
11	Fang X and Sweeney G: Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. Biochem Soc Trans. 34:798–801. 2006. View Article : Google Scholar : PubMed/NCBI
12	Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, Lopez BL, Koch W, Chan L, Goldstein BJ and Ma XL: Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation. 115:1408–1416. 2007. View Article : Google Scholar : PubMed/NCBI
13	Kim JE, Song SE, Kim YW, Kim JY, Park SC, Park YK, Baek SH, Lee IK and Park SY: Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: Involvement of cAMP/protein kinase A and AMP-activated protein kinase. J Endocrinol. 207:35–44. 2010. View Article : Google Scholar : PubMed/NCBI
14	Wei CD, Li Y, Zheng HY, Sun KS, Tong YQ, Dai W, et al: Globular adiponectin protects H9c2 cells from palmitate-induced apoptosis via Akt and ERK1/2 signaling pathways. Lipids Health Dis. 11:1352012. View Article : Google Scholar : PubMed/NCBI
15	Yan W, Zhang H, Liu P, Wang H, Liu J, Gao C, Liu Y, Lian K, Yang L, Sun L, et al: Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1α signaling contributing to increased vulnerability in diabetic heart. Basic Res Cardiol. 108:3292013. View Article : Google Scholar
16	Kim JE, Ahn MW, Baek SH, Lee IK, Ki YW, Kim JY, Dan JM and Park SY: AMPK activator, AICAR, inhibits palmitate-induced apoptosis in osteoblast. Bone. 43:394–404. 2008. View Article : Google Scholar : PubMed/NCBI
17	Krysko DV, Vanden Berghe T, D'Herde K and Vandenabeele P: Apoptosis and necrosis: Detection, discrimination and phagocytosis. Methods. 44:205–221. 2008. View Article : Google Scholar : PubMed/NCBI
18	Radad K, Rausch WD and Gille G: Rotenone induces cell death in primary dopaminergic culture by increasing ROS production and inhibiting mitochondrial respiration. Neurochem Int. 49:379–386. 2006. View Article : Google Scholar : PubMed/NCBI
19	Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS and Tannenbaum SR: Analysis of nitrate, nitrite and 15 N.nitrate in biological fluids. Anal Biochem. 126:131–138. 1982. View Article : Google Scholar : PubMed/NCBI
20	Akao M, Ohler A, O'Rourke B and Marbán E: Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells. Circ Res. 88:1267–1275. 2001. View Article : Google Scholar : PubMed/NCBI
21	Yeh ST, Guo HR, Su YS, Lin HJ, Hou CC, Chen HM, Chang MC and Wang YJ: Protective effects of N-acetylcysteine treatment post acute paraquat intoxication in rats and in human lung epithelial cells. Toxicology. 223:181–190. 2006. View Article : Google Scholar : PubMed/NCBI
22	Onyon LJ and Volans GN: The epidemiology and prevention of paraquat poisoning. Hum Toxicol. 6:19–29. 1987. View Article : Google Scholar : PubMed/NCBI
23	Gaudreault P, Karl PI and Friedman PA: Paraquat and putrescine uptake by lung slices of fetal and newborn rats. Drug Metab Dispos. 12:550–552. 1984.PubMed/NCBI
24	Wang GY, Hirai K and Shimada H: Mitochondrial breakage induced by the herbicide paraquat in cultured human lung cell. J Electron Microsc (Tokyo). 3:181–184. 1992.
25	Chen YW, Yang YT, Hung DZ, Su CC and Chen KL: Paraquat induces lung alveolar epithelial cell apoptosis via Nrf-2-regulated mitochondrialdysfunction and ER stress. Arch Toxicol. 86:1547–58. 2012. View Article : Google Scholar : PubMed/NCBI
26	Shokrzadeh M, Shaki F, Mohammadi E, Rezagholizadeh N and Ebrahimi F: Edaravone decreases paraquat toxicity in a549 cells and lung isolated mitochondria. Iran J Pharm Res. 13:675–681. 2014.PubMed/NCBI
27	Chang X, Lu W, Dou T, Wang X, Lou D, Sun X, et al: Paraquat inhibits cell viability via enhanced oxidative stress and apoptosis in human neural progenitor cells. Chem Biol Interact. 206:248–255. 2013. View Article : Google Scholar : PubMed/NCBI
28	Huang CL, Lee YC, Yang YC, Kuo TY and Huang NK: Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction. Toxicol Lett. 209:203–210. 2012. View Article : Google Scholar : PubMed/NCBI
29	Helewski KJ, Kowalczyk-Ziomek GI and Konecki J: Apoptosis and necrosis-two different ways leading to the same target. Wiad Lek. 59:679–684. 2006.In Polish.
30	Kasahara A and Scorrano L: Mitochondria: From cell death executioners to regulators of cell differentiation. Trends Cell Biol. 24:761–770. 2014. View Article : Google Scholar : PubMed/NCBI
31	Wang Z, Wang J, Xie R, Liu R and Lu Y: Mitochondria-derived reactive oxygen species play an important role in Doxorubicin-induced platelet apoptosis. Int J Mol Sci. 16:11087–11100. 2015. View Article : Google Scholar : PubMed/NCBI
32	Park M, Youn B, Zheng XL, Wu D, Xu A and Sweeney G: Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis. PLoS One. 6:e191432011. View Article : Google Scholar : PubMed/NCBI
33	Lin Z, Wu F, Lin S, Pan X, Jin L, Lu T, Shi L, Wang Y, Xu A and Li X: Adiponectin protects against acetaminophen-induced mitochondrial dysfunction and acute liver injury by promoting autophagy in mice. J Hepatol. 61:825–831. 2014. View Article : Google Scholar : PubMed/NCBI
34	Zheng A, Li H, Xu J, Cao K, Li H, Pu W, Yang Z, Peng Y, Long J, Liu J and Feng Z: Hydroxytyrosol improves mitochondrial function and reduces oxidative stress in the brain of db/db mice: Role of AMP-activated protein kinase activation. Br J Nutr. 113:1667–1676. 2015. View Article : Google Scholar : PubMed/NCBI
35	Chen H, Wang JP, Santen RJ and Yue W: Adenosine monophosphate activated protein kinase (AMPK), a mediator of estradiol-induced apoptosis in long-term estrogen deprived breast cancer cells. Apoptosis. 20:821–830. 2015. View Article : Google Scholar : PubMed/NCBI
36	Chen LJ, Na R, Gu M and Ran QT: Reduction in mitochondria H2O2 protects against insulin resistance through a mechanism of Akt and AMPK activation. Free Radic Biol Med. 47:S852009.
37	Pan JS, Huang L, Belousova T, Lu L, Yang Y, Reddel R, Chang A, Ju H, DiMattia G, Tong Q, et al: Stanniocalcin-1 inhibits renal ischemia/reperfusion injury via an AMP-activated protein kinase-dependent pathway. J Am Soc Nephrol. 26:364–378. 2015. View Article : Google Scholar :
38	Wu SB, Wu YT, Wu TP and Wei YH: Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress. Biochim Biophys Acta. 1840.1331–1344. 2014.
39	Qiao LP, Kinney B, Yoo HS, Lee B, Schaack J and Shao JH: Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1. Diabetes. 61:1463–1470. 2012. View Article : Google Scholar : PubMed/NCBI
40	Zhou M, Xu A, Tam PK, Lam KS, Chan L, Hoo RL, Liu J, Chow KH and Wang Y: Mitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury. Hepatology. 48:1087–1096. 2008. View Article : Google Scholar : PubMed/NCBI
41	Yamauchi T, Iwabu M, Okada-Iwabu M and Kadowaki T: Adiponectin receptors: A review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 28:15–23. 2014. View Article : Google Scholar : PubMed/NCBI