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Hexavalent Chromium Causes Apoptosis and Autophagy by Inducing Mitochondrial Dysfunction and Oxidative Stress in Broiler Cardiomyocytes

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Abstract

Hexavalent chromium (Cr(VI)) is a common environmental pollutant, which has a strong toxic effect on humans and animals. However, the cardiac toxicity of Cr(VI) in broilers remains to be explored. The development of heart disease is often linked to mitochondrial dysfunction especially exposure to toxic substances. In order to investigate the role of mitochondrial dysfunction in apoptosis and autophagy of broiler cardiomyocytes induced by hexavalent chromium, broiler cardiomyocytes were cultured in potassium dichromate of 0 mM, 16 mM, and 32 mM medium for 24 h. The results showed that, compared with the control group, reactive oxygen species (ROS) and apoptosis rate in the Cr(VI) treatment group increased in a dose-dependent manner, the mRNA levels of apoptosis-related genes Bax and p53 were significantly increased, and the mRNA level of Bcl-2 was significantly decreased. Compared with the control group, the mRNA level of autophagy-related genes (LC3-I, LC3-II, and Beclin1) in the Cr(VI) treatment group was significantly increased, the mRNA level of mTOR was significantly decreased, and the protein level of p62/SQSTM1 was significantly decreased. The protein level of Beclin1 and the ratio of LC3-II/LC3-I significantly increased. In addition, compared with the control group, mitochondrial membrane potential decreased in a dose-dependent manner, and mitochondrial dynamics–related genes SIRT1, SIRT3, and Mfn2 mRNA decreased significantly in the Cr(VI) treatment group. In this study, we concluded that Cr(VI) could cause broiler myocardial apoptosis and autophagy by inducing mitochondrial dysfunction and oxidative stress.

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References

  1. Welling R, Beaumont JJ, Petersen SJ, Alexeeff GV, Steinmaus C (2015) Chromium VI and stomach cancer: a meta-analysis of the current epidemiological evidence. Occup Environ Med 72:151–159. https://doi.org/10.1136/oemed-2014-102178

    Article  PubMed  Google Scholar 

  2. Hill R, Leidal AM, Madureira PA, Gillis LD, Cochrane HK, Waisman DM, Chiu A, Lee PW (2008) Hypersensitivity to chromium-induced DNA damage correlates with constitutive deregulation of upstream p53 kinases in p21-/- HCT116 colon cancer cells. DNA Repair (Amst) 7:239–252. https://doi.org/10.1016/j.dnarep.2007.10.001

    Article  CAS  Google Scholar 

  3. Kim D, Dai J, Fai LY, Yao H, Son YO, Wang L, Pratheeshkumar P, Kondo K, Shi X, Zhang Z (2015) Constitutive activation of epidermal growth factor receptor promotes tumorigenesis of Cr(VI)-transformed cells through decreased reactive oxygen species and apoptosis resistance development. J Biol Chem 290:2213–2224. https://doi.org/10.1074/jbc.M114.619783

    Article  CAS  PubMed  Google Scholar 

  4. Buters J, Biedermann T (2017) Chromium(VI) contact dermatitis: getting closer to understanding the underlying mechanisms of toxicity and sensitization! J Invest Dermatol 137:274–277. https://doi.org/10.1016/j.jid.2016.11.015

    Article  CAS  PubMed  Google Scholar 

  5. Bojarski B, Buchko O, Kondera E, Lugowska K, Osikowski A, Trela M, Witeska M, Lis MW (2021) Effects of embryonic exposure to chromium (VI) on blood parameters and liver microstructure of 1-day-old chickens. Poult Sci 100:366–371. https://doi.org/10.1016/j.psj.2020.10.016

    Article  CAS  PubMed  Google Scholar 

  6. Suljevic D, Sulejmanovic J, Focak M, Halilovic E, Pupalovic D, Hasic A, Alijagic A (2021) Assessing hexavalent chromium tissue-specific accumulation patterns and induced physiological responses to probe chromium toxicity in Coturnix japonica quail. Chemosphere 266:129005. https://doi.org/10.1016/j.chemosphere.2020.129005

    Article  CAS  PubMed  Google Scholar 

  7. Wang Y, Hao J, Zhang S, Li L, Wang R, Zhu Y, Liu Y, Liu J (2020) Inflammatory injury and mitophagy induced by Cr(VI) in chicken liver. Environ Sci Pollut Res Int 27:22980–22988. https://doi.org/10.1007/s11356-020-08544-3

    Article  CAS  PubMed  Google Scholar 

  8. Zhao Y, Zhang H, Wu X, Zhang T, Shen K, Li L, Peng Y, Mehmood K, Zhou D (2019) Metabonomic analysis of the hepatic injury suffer from hexavalent chromium poisoning in broilers. Environ Sci Pollut Res Int 26:18181–18190. https://doi.org/10.1007/s11356-019-05075-4

    Article  CAS  PubMed  Google Scholar 

  9. Sielski J, Kazirod-Wolski K, Jozwiak MA, Jozwiak M (2021) The influence of air pollution by PM2.5, PM10 and associated heavy metals on the parameters of out-of-hospital cardiac arrest. Sci Total Environ 788:147541. https://doi.org/10.1016/j.scitotenv.2021.147541

    Article  CAS  PubMed  Google Scholar 

  10. Yang D, Yang Q, Fu N, Li S, Han B, Liu Y, Tang Y, Guo X, Lv Z, Zhang Z (2021) Hexavalent chromium induced heart dysfunction via Sesn2-mediated impairment of mitochondrial function and energy supply. Chemosphere 264:128547. https://doi.org/10.1016/j.chemosphere.2020.128547

    Article  CAS  PubMed  Google Scholar 

  11. Zhunina OA, Yabbarov NG, Grechko AV, Starodubova AV, Ivanova E, Nikiforov NG, Orekhov AN (2021) The role of mitochondrial dysfunction in vascular disease, tumorigenesis, and diabetes. Front Mol Biosci 8:671908. https://doi.org/10.3389/fmolb.2021.671908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kowaltowski AJ, Vercesi AE (1999) Mitochondrial damage induced by conditions of oxidative stress. Free Radic Biol Med 26:463–471. https://doi.org/10.1016/s0891-5849(98)00216-0

    Article  CAS  PubMed  Google Scholar 

  13. Li J, Zheng X, Ma X, Xu X, Du Y, Lv Q, Li X, Wu Y, Sun H, Yu L, Zhang Z (2019) Melatonin protects against chromium(VI)-induced cardiac injury via activating the AMPK/Nrf2 pathway. J Inorg Biochem 197:110698. https://doi.org/10.1016/j.jinorgbio.2019.110698

    Article  CAS  PubMed  Google Scholar 

  14. Lu J, Liu K, Qi M, Geng H, Hao J, Wang R, Zhao X, Liu Y, Liu J (2019) Effects of Cr(VI) exposure on electrocardiogram, myocardial enzyme parameters, inflammatory factors, oxidative kinase, and ATPase of the heart in Chinese rural dogs. Environ Sci Pollut Res Int 26:30444–30451. https://doi.org/10.1007/s11356-019-06253-0

    Article  CAS  PubMed  Google Scholar 

  15. Liang Q, Zhang Y, Huang M, Xiao Y, Xiao F (2019) Role of mitochondrial damage in Cr(VI)induced endoplasmic reticulum stress in L02 hepatocytes. Mol Med Rep 19:1256–1265. https://doi.org/10.3892/mmr.2018.9704

    Article  CAS  PubMed  Google Scholar 

  16. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pattingre S, Tassa A, Qu XP, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939. https://doi.org/10.1016/j.cell.2005.07.002

    Article  CAS  PubMed  Google Scholar 

  18. Zheng XY, Li SY, Li JY, Lv YY, Wang XQ, Wu PF, Yang QY, Tang YQ, Liu Y, Zhang ZG (2020) Hexavalent chromium induces renal apoptosis and autophagy via disordering the balance of mitochondrial dynamics in rats. Ecotoxicol Environ Saf 204:9. https://doi.org/10.1016/j.ecoenv.2020.111061

    Article  CAS  Google Scholar 

  19. Li H, Zhang J, Xia Y, Pan W, Zhou D (2021) Antagonistic effect of nano-selenium on hepatocyte apoptosis induced by DEHP via PI3K/AKT pathway in chicken liver. Ecotoxicol Environ Saf 218:112282. https://doi.org/10.1016/j.ecoenv.2021.112282

    Article  CAS  PubMed  Google Scholar 

  20. El-Demerdash FM, El-Sayed RA, Abdel-Daim MM (2021) Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats. J Trace Elem Med Biol 67:126791. https://doi.org/10.1016/j.jtemb.2021.126791

    Article  CAS  PubMed  Google Scholar 

  21. Li X, He S, Zhou J, Yu X, Li L, Liu Y, Li W (2021) Cr (VI) induces abnormalities in glucose and lipid metabolism through ROS/Nrf2 signaling. Ecotoxicol Environ Saf 219:112320. https://doi.org/10.1016/j.ecoenv.2021.112320

    Article  CAS  PubMed  Google Scholar 

  22. Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950. https://doi.org/10.1152/physrev.00026.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990. https://doi.org/10.1016/j.cellsig.2012.01.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhu Y, Wang L, Yu X, Jiang S, Wang X, Xing Y, Guo S, Liu Y, Liu J (2021) Cr(VI) promotes tight joint and oxidative damage by activating the Nrf2/ROS/Notch1 axis. Environ Toxicol Pharmacol 85:103640. https://doi.org/10.1016/j.etap.2021.103640

    Article  CAS  PubMed  Google Scholar 

  25. Dhalla NS, Temsah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18:655–673. https://doi.org/10.1097/00004872-200018060-00002

    Article  CAS  PubMed  Google Scholar 

  26. Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145–1159. https://doi.org/10.1016/j.cell.2012.02.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Leuner K, Schulz K, Schuett T, Pantel J, Prvulovic D, Rhein V, Savaskan E, Czech C, Eckert A, Mueller WE (2012) Peripheral mitochondrial dysfunction in Alzheimer’s disease: focus on lymphocytes. Mol Neurobiol 46:194–204. https://doi.org/10.1007/s12035-012-8300-y

    Article  CAS  PubMed  Google Scholar 

  28. Xu G, Liu S, Huang M, Jiang X, Yang M (2021) Cadmium induces apoptosis of human granulosa cell line KGN via mitochondrial dysfunction-mediated pathways. Ecotoxicol Environ Saf 220:112341–112341. https://doi.org/10.1016/j.ecoenv.2021.112341

    Article  CAS  PubMed  Google Scholar 

  29. Wang C, Chen J, Wang M, Naruse K, Takahashi K (2021) Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress. Biochem Biophys Res Commun 566:190–196. https://doi.org/10.1016/j.bbrc.2021.03.077

    Article  CAS  PubMed  Google Scholar 

  30. Xu Y, Wang X, Geng N, Zhu Y, Zhang S, Liu Y, Liu J (2020) Mitophagy is involved in chromium (VI)-induced mitochondria damage in DF-1 cells. Ecotoxicol Environ Saf 194:110414. https://doi.org/10.1016/j.ecoenv.2020.110414

    Article  CAS  PubMed  Google Scholar 

  31. Yang L, Chen Y, Zhou J, Sun J, Jiang W, Liu T, Rao C, Pan X (2021) Aconitine induces mitochondrial energy metabolism dysfunction through inhibition of AMPK signaling and interference with mitochondrial dynamics in SH-SY5Y cells. Toxicol Lett 347:36–44. https://doi.org/10.1016/j.toxlet.2021.04.020

    Article  CAS  PubMed  Google Scholar 

  32. Han B, Li S, Lv Y, Yang D, Li J, Yang Q, Wu P, Lv Z, Zhang Z (2019) Dietary melatonin attenuates chromium-induced lung injury via activating the Sirt1/Pgc-1alpha/Nrf2 pathway. Food Funct 10:5555–5565. https://doi.org/10.1039/c9fo01152h

    Article  CAS  PubMed  Google Scholar 

  33. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656. https://doi.org/10.1038/nrc883

    Article  CAS  PubMed  Google Scholar 

  34. Obeng E (2021) Apoptosis (programmed cell death) and its signals - a review. Braz J Biol 81:1133–1143. https://doi.org/10.1590/1519-6984.228437

    Article  CAS  PubMed  Google Scholar 

  35. Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075. https://doi.org/10.1038/nature06639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhang S, Zhao X, Hao J, Zhu Y, Wang Y, Wang L, Guo S, Yi H, Liu Y, Liu J (2021) The role of ATF6 in Cr(VI)-induced apoptosis in DF-1 cells. J Hazard Mater 410:124607. https://doi.org/10.1016/j.jhazmat.2020.124607

    Article  CAS  PubMed  Google Scholar 

  37. Fu SC, Liu JM, Lee KI, Tang FC, Fang KM, Yang CY, Su CC, Chen HH, Hsu RJ, Chen YW (2020) Cr(VI) induces ROS-mediated mitochondrial-dependent apoptosis in neuronal cells via the activation of Akt/ERK/AMPK signaling pathway. Toxicol In Vitro 65:104795. https://doi.org/10.1016/j.tiv.2020.104795

    Article  CAS  PubMed  Google Scholar 

  38. Hao J, Song Y, Tian B, Qi C, Li L, Wang L, Xing Y, Zhao X, Liu J (2020) Platycodon grandifloras polysaccharides inhibit mitophagy injury induced by Cr (VI) in DF-1 cells. Ecotoxicol Environ Saf 202:110901. https://doi.org/10.1016/j.ecoenv.2020.110901

    Article  CAS  PubMed  Google Scholar 

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Funding

This research was funded by the Fundamental Research Funds for the Central Universities, grant number 2662020DKPY013; the National Natural Science Foundation of China, grant number 31972748; and the National Key R&D Program of China, grant number 2016YFD0501208.

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Authors and Affiliations

  1. College of Veterinary Medicine, Veterinary clincal medicine laboratory, Huazhong Agricultural University, 1 Shizishan Street, Wuhan, CA, 430070, People’s Republic of China

    Hao Li, Jingjing Shi, Haihang Gao, Xiaoqi Yang, Yang Fu, Ying Xia & Donghai Zhou

  2. Hainan College of Vocation and Technique, No.95 Nanhai Avenue, Longhua District, Haikou City, 570105, Hainan, China

    Yuxuan Peng

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  1. Hao Li
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  2. Jingjing Shi
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  3. Haihang Gao
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  4. Xiaoqi Yang
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  5. Yang Fu
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  7. Ying Xia
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  8. Donghai Zhou
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Contributions

HL conceived and designed the experiments; HL, JS, HG, XY, YF, YP, and YX contributed in the sample collection and reagent preparation; LH wrote the manuscript; DZ provided technical guidance and experimental funding. All the authors were involved in discussing the contents of the manuscript and agreed for publication.

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Correspondence to Donghai Zhou.

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Li, H., Shi, J., Gao, H. et al. Hexavalent Chromium Causes Apoptosis and Autophagy by Inducing Mitochondrial Dysfunction and Oxidative Stress in Broiler Cardiomyocytes. Biol Trace Elem Res 200, 2866–2875 (2022). https://doi.org/10.1007/s12011-021-02877-x

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