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Hydrogen-Rich Medium Regulates Cr(VI)-Induced ER Stress and Autophagy Signaling in DF-1 Cells

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Abstract

Related studies have shown that chromium (Cr) is toxic to cells, and hydrogen can protect cells by regulating endoplasmic reticulum (ER) stress and autophagy. However, there are few reports on the protective effects of hydrogen on heavy metal-induced cell damage. The objective of this study was to investigate the protection of hydrogen-rich medium (HRM) on Cr(VI)-induced ER stress and autophagy in DF-1 cells. Therefore, HRM were pretreated for 30 min before Cr(VI) treatment, and detected the autophagy and ER stress-related indicators to determine the role of HRM. The results showed that HRM could reduce the cell damage caused by Cr(VI), and 3-methyladenine (3-MA) could protect cells by inhibiting over autophagy. HRM can reverse the changes of ER stress- and autophagy-related indexes caused by Cr(VI), and inhibit the excessive autophagy caused by Cr(VI). In conclusion, HRM can protect cells from damage induced by Cr(VI), and play a role by inhibiting ER stress-mediated autophagy.

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References

  1. Krebs J, Agellon LB, Michalak M (2015) Ca2+ homeostasis and endoplasmic reticulum (ER) stress: an integrated view of calcium signaling. Biochem Biophys Res Commun 460:114–121

    Article  CAS  PubMed  Google Scholar 

  2. Zhang C, Jia X, Wang K, Bao J, Li P, Chen M, Wan JB, Su H, Mei Z, He C (2016) Polyphyllin VII induces an autophagic cell death by activation of the JNK pathway and inhibition of PI3K/AKT/mTOR pathway in HepG2 cells. PLoS One 11:e0147405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454:455–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chen P, Geng N, Zhou D, Zhu Y, Xu Y, Liu K, Liu Y, Liu J (2019) The regulatory role of COX-2 in the interaction between Cr(VI)-induced endoplasmic reticulum stress and autophagy in DF-1 cells. Ecotoxicol Environ Saf 170:112–119

    Article  CAS  PubMed  Google Scholar 

  5. Fouillet A, Levet C, Virgone A, Robin M, Dourlen P, Rieusset J, Belaidi E, Ovize M, Touret M, Nataf S, Mollereau B (2012) ER stress inhibits neuronal death by promoting autophagy. Autophagy 8:915–926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lee WS, Yoo WH, Chae HJ (2015) ER stress and autophagy. Curr Mol Med 15:735–745

    Article  CAS  PubMed  Google Scholar 

  7. Periyasamy P, Guo ML, Buch S (2016) Cocaine induces astrocytosis through ER stress-mediated activation of autophagy. Autophagy 12:1310–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wang Z, Yin F, Xu J, Zhang T, Wang G, Mao M, Wang Z, Sun W, Han J, Yang M, Jiang Y, Hua Y, Cai Z (2019) CYT997(Lexibulin) induces apoptosis and autophagy through the activation of mutually reinforced ER stress and ROS in osteosarcoma. J Exp Clin Cancer Res: CR 38:44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cao J, Ying M, Xie N, Lin G, Dong R, Zhang J, Yan H, Yang X, He Q, Yang B (2014) The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-hpr: autophagy or apoptosis? Antioxid Redox Signal 21:1443–1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang H, Wen Y, Zhang M, Liu Q, Zhang H, Zhang J, Lu L, Ye T, Bai X, Xiao G, Wang M (2020) MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint. Autophagy 16:271–288

    Article  CAS  PubMed  Google Scholar 

  11. Rami A, Kögel D (2008) Apoptosis meets autophagy-like cell death in the ischemic penumbra: two sides of the same coin? Autophagy 4:422–426

    Article  CAS  PubMed  Google Scholar 

  12. Wang SH, Shih YL, Ko WC, Wei YH, Shih CM (2008) Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cell Mol Life Sci: CMLS 65:3640–3652

    Article  CAS  PubMed  Google Scholar 

  13. Xie N, Geng N, Zhou D, Xu Y, Liu K, Liu Y, Liu J (2019) Protective effects of anthocyanin against apoptosis and oxidative stress induced by arsanilic acid in DF-1 cells. Mol Biol Rep 46:301–308

    Article  CAS  PubMed  Google Scholar 

  14. Hussain S, Al-Nsour F, Rice AB, Marshburn J, Yingling B, Ji Z, Zink JI, Walker NJ, Garantziotis S (2012) Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes. ACS Nano 6:5820–5829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Obermoser V, Baecker D, Schuster C, Braun V, Kircher B, Gust R (2018) Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents. Dalton transactions (Cambridge, England: 2003) 47:4341–4351

    Article  CAS  Google Scholar 

  16. Yazawa T, Imamichi Y, Yuhki K.c, Uwada J, Taniguchi T (2019) Cyclooxygenaseis acutely induced by CCAAT/enhancer-binding protein β to produce prostaglandin E 2 and F 2α following gonadotropin stimulation in Leydig cells. Mol Reprod Dev 86:786–797

    Article  CAS  PubMed  Google Scholar 

  17. Xu W, Huang Y, Zhang T, Zhao L, Fan J, Li L (2018) Cyclooxygenase-2 gene polymorphisms and susceptibility to hepatocellular carcinoma: a meta-analysis based on 10 case-control studies. J Cancer Res Ther 14:S105-s113

    Article  CAS  PubMed  Google Scholar 

  18. Jin J, Zhao L, Zou W, Shen W, Zhang H, He Q (2018) Activation of cyclooxygenase-2 by ATF4 during endoplasmic reticulum stress regulates kidney podocyte autophagy induced by lupus nephritis. Cellular Physiol Biochem: Int J Exp Cell Physiol Biochem Pharmacol 48:753–764

    Article  CAS  Google Scholar 

  19. Krumschnabel G, Nawaz M (2004) Acute toxicity of hexavalent chromium in isolated teleost hepatocytes. Aquat Toxicol (Amsterdam, Netherlands) 70:159–167

    Article  CAS  Google Scholar 

  20. Thompson CM, Kirman CR, Proctor DM, Haws LC, Suh M, Hays SM, Hixon JG, Harris MA (2014) A chronic oral reference dose for hexavalent chromium-induced intestinal cancer. J Appl Toxicol: JAT 34:525–536

    Article  CAS  PubMed  Google Scholar 

  21. Wise JP Sr, Payne R, Wise SS, LaCerte C, Wise J, Gianios C Jr, Thompson WD, Perkins C, Zheng T, Zhu C, Benedict L, Kerr I (2009) A global assessment of chromium pollution using sperm whales (Physeter macrocephalus) as an indicator species. Chemosphere 75:1461–1467

    Article  CAS  PubMed  Google Scholar 

  22. Wu F, Sun H, Kluz T, Clancy HA, Kiok K, Costa M (2012) Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol 258:166–175

    Article  CAS  PubMed  Google Scholar 

  23. Myers JM, Antholine WE, Myers CR (2011) The intracellular redox stress caused by hexavalent chromium is selective for proteins that have key roles in cell survival and thiol redox control. Toxicology 281:37–47

    Article  CAS  PubMed  Google Scholar 

  24. Yang F, Zhao L, Mei D, Jiang L, Geng C, Li Q, Yao X, Liu Y, Kong Y, Cao J (2017) HMGA2 plays an important role in Cr (VI)-induced autophagy. Int J Cancer 141:986–997

    Article  CAS  PubMed  Google Scholar 

  25. Ge H, Li Z, Jiang L, Li Q, Geng C, Yao X, Shi X, Liu Y, Cao J (2019) Cr (VI) induces crosstalk between apoptosis and autophagy through endoplasmic reticulum stress in A549 cells. Chem Biol Interact 298:35–42

    Article  CAS  PubMed  Google Scholar 

  26. Jiang X, Niu X, Guo Q, Dong Y, Xu J, Yin N, Qi Q, Jia Y, Gao L, He Q, Lv P (2019) FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia. Behav Brain Res 356:98–106

    Article  CAS  PubMed  Google Scholar 

  27. Wang W, Tian L, Li Y, Wang X, Xia F, Li L, Li J, Zhang Z (2013) Effects of hydrogen-rich saline on rats with acute carbon monoxide poisoning. J Emerg Med 44:107–115

    Article  PubMed  Google Scholar 

  28. Pan Z, Zhao Y, Yu H, Liu D, Xu H (2015) Effect of hydrogen-rich saline on cardiomyocyte autophagy during myocardial ischemia-reperfusion in aged rats. Zhonghua Yi Xue Za Zhi 95:2022–2026

    CAS  PubMed  Google Scholar 

  29. Yue L, Li H, Zhao Y, Li J, Wang B (2015) Effects of hydrogen-rich saline on Akt/GSK3β signaling pathways and cardiac function during myocardial ischemia-reperfusion in rats. Zhonghua Yi Xue Za Zhi 95:1483–1487

    CAS  PubMed  Google Scholar 

  30. Zhao Y, Tang Y, Suo C, Liu D, Li S, Li H (2014) Effects of hydrogen-rich saline on endoplasmic reticulum stress during myocardial ischemia-reperfusion in rats. Zhonghua Yi Xue Za Zhi 94:3024–3028

    CAS  PubMed  Google Scholar 

  31. Zhang Y, Long Z, Xu J, Tan S, Zhang N, Li A, Wang L, Wang T (2017) Hydrogen inhibits isoproterenol-induced autophagy in cardiomyocytes in vitro and in vivo. Mol Med Rep 16:8253–8258

    Article  CAS  PubMed  Google Scholar 

  32. Geng N, Wang X, Yu X, Wang R, Zhu Y, Zhang M, Liu J, Liu Y (2020) Staphylococcus aureus avoids autophagy clearance of bovine mammary epithelial cells by impairing lysosomal function. Front Immunol 11:746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu K, Chen P, Lu J, Zhu Y, Xu Y, Liu Y, Liu J (2020) Protective effect of purple tomato anthocyanidin on chromium(VI)-induced autophagy in LMH cells by inhibiting endoplasmic reticulum stress. Biol Trace Elem Res 194:570–580

    Article  CAS  PubMed  Google Scholar 

  34. Cerezo M, Rocchi S (2017) New anti-cancer molecules targeting HSPA5/BIP to induce endoplasmic reticulum stress, autophagy and apoptosis. Autophagy 13:216–217

    Article  CAS  PubMed  Google Scholar 

  35. Jeon H, Im GI (2017) Autophagy in osteoarthritis. Connect Tissue Res 58:497–508

    Article  CAS  PubMed  Google Scholar 

  36. Wirawan E, Vande Walle L, Kersse K, Cornelis S, Claerhout S, Vanoverberghe I, Roelandt R, De Rycke R, Verspurten J, Declercq W, Agostinis P, VandenBerghe T, Lippens S, Vandenabeele P (2010) Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis 1:e18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Komatsu M, Ichimura Y (2010) Physiological significance of selective degradation of p62 by autophagy. FEBS Lett 584:1374–1378

    Article  CAS  PubMed  Google Scholar 

  38. Myers CR (2012) The effects of chromium(VI) on the thioredoxin system: implications for redox regulation. Free Radical Biol Med 52:2091–2107

    Article  CAS  Google Scholar 

  39. Zuo Z, Cai T, Li J, Zhang D, Yu Y, Huang C (2012) Hexavalent chromium Cr(VI) up-regulates COX-2 expression through an NFκB/c-Jun/AP-1-dependent pathway. Environ Health Perspect 120:547–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang Y, Xiao F, Liu X, Liu K, Zhou X, Zhong C (2017) Cr(VI) induces cytotoxicity in vitro through activation of ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction via the PI3K/Akt signaling pathway. Toxicol In Vitro: Int J Publ Assoc Bibra 41:232–244

    Article  CAS  Google Scholar 

  41. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2:326–332

    Article  CAS  PubMed  Google Scholar 

  42. Schröder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789

    Article  CAS  PubMed  Google Scholar 

  43. Hong SH, Chang SH, Cho KC, Kim S, Park S, Lee AY, Jiang HL, Kim HJ, Lee S, Yu KN, Seo HW, Chae C, Kim KP, Park J, Cho MH (2016) Endoplasmic reticulum-Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy. Oncotarget 7:65335–65347

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ji C, Zhang Z, Chen L, Zhou K, Li D, Wang P, Huang S, Gong T, Cheng B (2016) Endoplasmic reticulum stress-induced autophagy determines the susceptibility of melanoma cells to dabrafenib. Drug Des Dev Ther 10:2491–2498

    Article  CAS  Google Scholar 

  45. Feng D, Wang L, Wang N, Abraham K, Tao L, Huang W, Shi Y, Dong Y, Yan Q (2017) Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings. J Pineal Res 62:1–13

  46. Hart LS, Cunningham JT, Datta T, Dey S, Tameire F, Lehman SL, Qiu B, Zhang H, Cerniglia G, Bi M, Li Y, Gao Y, Liu H, Li C, Maity A, Thomas-Tikhonenko A, Perl AE, Koong A, Fuchs SY, Diehl JA, Mills IG, Ruggero D, Koumenis C (2012) ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Investig 122:4621–4634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lee J, Yang G, Kim YJ, Tran QH, Choe W, Kang I, Kim SS, Ha J (2017) Hydrogen-rich medium protects mouse embryonic fibroblasts from oxidative stress by activating LKB1-AMPK-FoxO1 signal pathway. Biochem Biophys Res Commun 491:733–739

    Article  CAS  PubMed  Google Scholar 

  48. Zhang Y, Xu J, Long Z, Wang C, Wang L, Sun P, Li P, Wang T (2016) Hydrogen (H(2)) inhibits isoproterenol-induced cardiac hypertrophy via antioxidative pathways. Front Pharmacol 7:392

    PubMed  PubMed Central  Google Scholar 

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Funding

This project was supported by the Key Research and Development Program of Shandong Province (Important Science and Technology Innovation Project) (2019JZZY010735), the National Nature Science Foundation of China (No. 31872535), and Shandong Natural Science Foundation of China (ZR2018MC027).

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Contributions

Conceptualization, Jianzhu Liu; data curation, Kangping Liu and Yukun Cui; formal analysis, Hongyan Li and Changxi Qi; investigation, Guodong Cheng; methodology, Shuhua Guo and Yuxiao Xing; project administration, Jianzhu Liu and Yongxia Liu; resources, Kangping Liu; software, Yukun Cui; supervision, Jianzhu Liu and Yongxia Liu; validation, Yuxiao Xing; visualization, Shuhua Guo; writing — original draft, Shuhua Guo and Yuxiao Xing; writing — review and editing, Jianzhu Liu.

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Correspondence to Yongxia Liu or Jianzhu Liu.

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The animal care and use procedures applied in the study were conducted under the protocols approved by the Institutional Animal Care and Use Committee of Shandong Agricultural University (SDAU 2019–047).

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Liu, K., Cui, Y., Li, H. et al. Hydrogen-Rich Medium Regulates Cr(VI)-Induced ER Stress and Autophagy Signaling in DF-1 Cells. Biol Trace Elem Res 200, 2329–2337 (2022). https://doi.org/10.1007/s12011-021-02850-8

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  • DOI: https://doi.org/10.1007/s12011-021-02850-8

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