Effect of endoplasmic reticulum calcium on paraquat‑induced apoptosis of human lung type II alveolar epithelial A549 cells

Song,Chun‑Qing; Sun,Da‑Zhuang; Xu,Yong‑Min; Yang,Chen; Cai,Quan; Dong,Xue‑Song

doi:10.3892/mmr.2019.10469

Effect of endoplasmic reticulum calcium on paraquat‑induced apoptosis of human lung type II alveolar epithelial A549 cells

Authors:
- Chun‑Qing Song
- Da‑Zhuang Sun
- Yong‑Min Xu
- Chen Yang
- Quan Cai
- Xue‑Song Dong
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Affiliations: Department of Emergency, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: July 4, 2019 https://doi.org/10.3892/mmr.2019.10469
Pages: 2419-2425

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Abstract

The present study aimed to explore the role of endoplasmic reticulum calcium (ER Ca2+) in the apoptosis of human lung type II alveolar epithelial A549 cells induced by paraquat (PQ) in vitro. PQ significantly elevated the intracellular Ca2+ concentration. Treatment with the Ca2+‑ATPase inhibitor thapsigargin significantly increased PQ‑induced cytotoxicity, elevated the intracellular level of Ca2+, and increased the apoptosis rate, the protein expression of glucose‑regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), and the activities of caspase‑7 and caspase‑12 in PQ‑treated cells. By contrast, treatment with heparin, an inositol 1,4,5‑triphosphate receptor inhibitor, remarkably attenuated cytotoxicity and decreased the intracellular level of Ca2+, the apoptosis rate and the expression levels of GRP78, CHOP and Caspases. In conclusion, PQ impaired the regulating function of ER Ca2+ and resulted in an excessive increase of intracellular Ca2+. Therefore, influencing the Ca2+ signaling in the ER influenced the apoptosis of A549 cells via the ER stress pathway.

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1	Serra A, Domingos F and Prata MM: Paraquat intoxication. Acta Med Port. 16:25–32. 2013.(In Portuguese).
2	Ko DR, Chung SP, You JS, Cho S, Park Y, Chun B, Moon J, Kim H, Kim YH, Kim HJ, et al: Effects of paraquat ban on herbicide poisoning-related mortality. Yonsei Med J. 58:859–866. 2017. View Article : Google Scholar : PubMed/NCBI
3	He Y, Zou L, Zhou Y, Hu H, Yao R, Jiang Y, Lau WB, Yuan T, Huang W, Zeng Z and Cao Y: Adiponectin ameliorates the apoptotic effects of paraquat on alveolar typecells via improvements in mitochondrial function. Mol Med Rep. 14:746–752. 2016. View Article : Google Scholar : PubMed/NCBI
4	Zhao G, Cao K, Xu C, Sun A, Lu W, Zheng Y, Li H, Hong G, Wu B, Qiu Q and Lu Z: Crosstalk between mitochondrial fission and oxidative stress in paraquat-induced apoptosis in mouse alveolar type II cells. Int J Biol Sci. 13:888–900. 2017. View Article : Google Scholar : PubMed/NCBI
5	Wang R, Sun DZ, Song CQ, Xu YM, Liu W, Liu Z and Dong XS: Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway. Toxicol In Vitro. 46:58–65. 2018. View Article : Google Scholar : PubMed/NCBI
6	Marchi S, Patergnani S, Missiroli S, Morciano G, Rimessi A, Wieckowski MR, Giorgi C and Pinton P: Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death. Cell Calcium. 69:62–72. 2018. View Article : Google Scholar : PubMed/NCBI
7	McIlwain DR, Berger T and Mak TW: Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 5:a0086562015.
8	Sehgal P, Szalai P, Olesen C, Praetorius HA, Nissen P, Christensen SB, Engedal N and Møller JV: Inhibition of the Sarco/endoplasmic reticulum (ER) Ca²⁺-ATPase by thapsigargin analogs induces cell death via ER Ca²⁺ depletion and the unfolded protein response. J Biol Chem. 292:19656–19673. 2017. View Article : Google Scholar : PubMed/NCBI
9	Hammadi M, Oulidi A, Gackière F, Katsogiannou M, Slomianny C, Roudbaraki M, Dewailly E, Delcourt P, Lepage G, Lotteau S, et al: Modulation of ER stress and apoptosis by endoplasmic reticulum calcium leak via translocon during unfolded protein response: Involvement of GRP78. FASEB J. 27:1600–1609. 2013. View Article : Google Scholar : PubMed/NCBI
10	Szikra T and Krizaj D: The dynamic range and domain-specific signals of intracellular calcium inphotoreceptors. Neuroscience. 141:143–155. 2006. View Article : Google Scholar : PubMed/NCBI
11	Zhivotovsky B and Orrenius S: Calcium and cell death mechanisms: A perspective from the cell death community. Cell Calcium. 50:211–221. 2011. View Article : Google Scholar : PubMed/NCBI
12	Shao X and Chen JH: Progress on pathogenesis and treatment of paraquat-induced pulmonary fibrosis. Zhejiang Da Xue Xue Bao Yi Xue Ban. 43:717–727. 2014.(In Chinese). PubMed/NCBI
13	Dinis-Oliveira RJ, Duarte JA, Sánchez-Navarro A, Remião F, Bastos ML and Carvalho F: Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol. 38:13–71. 2008. View Article : Google Scholar : PubMed/NCBI
14	Bursch W, Oberhammer F and Schulte-Hermann R: Cell death by apoptosis and its protective role against disease. Trends Pharmacol Sci. 13:245–251. 1992. View Article : Google Scholar : PubMed/NCBI
15	Evans VG: Multiple pathways to apoptosis. Cell Biol Int. 17:461–476. 1993. View Article : Google Scholar : PubMed/NCBI
16	Felsenfeld A, Rodriguez M and Levine B: New insights in regulation of calcium homeostasis. Curr Opin Nephrol Hypertens. 22:371–376. 2013. View Article : Google Scholar : PubMed/NCBI
17	Hajnóczky G, Davies E and Madesh M: Calcium signaling and apoptosis. Biochem Biophys Res Commun. 304:445–454. 2003. View Article : Google Scholar : PubMed/NCBI
18	Sun DP, Li XX, Liu XL, Zhao D, Qiu FQ, Li Y and Ma P: Gypenosides induce apoptosis by Ca²⁺ overload mediated by endoplasmic-reticulum and store-operated Ca²⁺ channels in human hepatoma cells. Cancer Biother Radiopharm. 28:320–326. 2013. View Article : Google Scholar : PubMed/NCBI
19	Orrenius S, Gogvadze V and Zhivotovsky B: Calcium and mitochondria in the regulation of cell death. Biochem Biophys Res Commun. 460:72–81. 2015. View Article : Google Scholar : PubMed/NCBI
20	Cho H, Wu M, Zhang L, Thompson R, Nath A and Chan C: Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells. BMC Syst Bio. 7:92013. View Article : Google Scholar
21	Guo G, Meng Y, Tan W, Xia Y, Cheng C, Chen X and Gu Z: Induction of apoptosis coupled to endoplasmic reticulum stress through regulation of CHOP and JNK in bone marrow mesenchymal stem cells from patients with systemic lupus erythematosus. J Immunol Res. 2015:1837382015. View Article : Google Scholar : PubMed/NCBI
22	Mills E, Chen X, Pham E, Wong S and Truong K: Engineering a photoactivated caspase-7 for rapid induction of apoptosis. ACS Synth Biol. 1:75–82. 2012. View Article : Google Scholar : PubMed/NCBI
23	Zhang Q, Liu J, Chen S, Liu J, Liu L, Liu G, Wang F, Jiang W, Zhang C, Wang S and Yuan X: Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress. Apoptosis. 21:432–442. 2016. View Article : Google Scholar : PubMed/NCBI
24	Zhang JY, Lin MT, Tung HY, Tang SL, Yi T, Zhang YZ, Tang YN, Zhao ZZ and Chen HB: Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway. Am J Cancer Res. 6:819–826. 2016.PubMed/NCBI
25	Lin M, Tang S, Zhang C, Chen H, Huang W, Liu Y and Zhang J: Euphorbia factor L2 induces apoptosis in A549 cells through the mitochondrial pathway. Acta Pharm Sin B. 7:59–64. 2017. View Article : Google Scholar : PubMed/NCBI