Skip to main content
Log in

Mitophagy Induced by Mitochondrial Function Damage in Chicken Kidney Exposed to Cr(VI)

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Cr(VI) is a heavy metal environmental pollutant and carcinogen. Excessive Cr(VI) exposure injures kidneys. This study aimed to investigate mitophagy induced by mitochondrial function damage in chicken kidney exposed to Cr(VI). To explore the mechanism involved, we randomly divided 40 one-day-old Hy-line Brown cockerels into four groups, with each group exposed to different concentrations of Cr(VI), i.e., 0, 10, 30 and 50 mg kg−1, which were orally administered daily for 45 days. Excessive Cr(VI) increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and chemokine (C-X-C motif) ligand 1(CXCL1) expression and decreased Ca2+-adenosine triphosphatase (Ca2+-ATPase), Mg2+-ATPase and Na+/k+-ATPase activities in chicken kidney. Furthermore, Cr(VI) significantly increased reactive oxygen species (ROS) production and induced mitochondrial membrane potential (MMP) collapse and typical autophagosome formation. With the increase of Cr(VI) concentration, the Parkin translocation, value of LC3-II increased and decreased the content of p62/SQSTM1 and the translocase of outer mitochondrial membrane 20 (TOMM20). In summary, our findings explicated that mitochondrial function damage and mitophagy-related indicators were related to Cr(VI) concentration in chicken kidney.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Kotyzova D, Hodková A, Bludovská M, Eybl V (2015) Effect of chromium (VI) exposure on antioxidant defense status and trace element homeostasis in acute experiment in rat. Toxicol Ind Health 31(11):1044–1050. https://doi.org/10.1177/0748233713487244

    Article  CAS  PubMed  Google Scholar 

  2. De Flora S, D'Agostini F, Balansky R, Micale R, Baluce B, Izzotti A (2008) Lack of genotoxic effects in hematopoietic and gastrointestinal cells of mice receiving chromium(VI) with the drinking water. Mutat Res 659(1–2):60–67. https://doi.org/10.1016/j.mrrev.2007.11.005

  3. Thatoi H, Das S, Mishra J, Rath BP, Das N (2014) Bacterial chromate reductase, a potential enzyme for bioremediation of hexavalent chromium: a review. J Environ Manag 146:383–399. https://doi.org/10.1016/j.jenvman.2014.07.014

    Article  CAS  Google Scholar 

  4. Roy RV, Pratheeshkumar P, Son YO, Wang L, Hitron JA, Divya SP, Zhang Z, Shi X (2016) Different roles of ROS and Nrf2 in Cr(VI)-induced inflammatory responses in normal and Cr(VI)-transformed cells. Toxicol Appl Pharmacol 307:81–90. https://doi.org/10.1016/j.taap.2016.07.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lag M, Rodionov D, Ovrevik J, Bakke O, Schwarze PE, Refsnes M (2010) Cadmium-induced inflammatory responses in cells relevant for lung toxicity: expression and release of cytokines in fibroblasts, epithelial cells and macrophages. Toxicol Lett 193(3):252–260. https://doi.org/10.1016/j.toxlet.2010.01.015

    Article  CAS  PubMed  Google Scholar 

  6. Dong GH, Zhang YH, Zheng L, Liang ZF, Jin YH, He QC (2012) Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice. Environ Toxicol 27(5):285–296. https://doi.org/10.1002/tox.20642

    Article  CAS  PubMed  Google Scholar 

  7. Park EJ, Park K (2009) Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett 184(1):18–25. https://doi.org/10.1016/j.toxlet.2008.10.012

    Article  CAS  PubMed  Google Scholar 

  8. Liu SQ, Wang LY, Liu GH, Tang DZ, Fan XX, Zhao JP, Jiao HC, Wang XJ, Sun SH, Lin H (2018) Leucine alters immunoglobulin a secretion and inflammatory cytokine expression induced by lipopolysaccharide via the nuclear factor-kappaB pathway in intestine of chicken embryos. Animal 12(9):1903–1911. https://doi.org/10.1017/s1751731117003342

    Article  CAS  PubMed  Google Scholar 

  9. Kim JH, Kang JC (2016) The toxic effects on the stress and immune responses in juvenile rockfish, Sebastes schlegelii exposed to hexavalent chromium. Environ Toxicol Pharmacol 43:128–133. https://doi.org/10.1016/j.etap.2016.03.008

    Article  CAS  PubMed  Google Scholar 

  10. Liang Q, Zhang Y, Zeng M, Guan L, Xiao Y, Xiao F (2018) The role of IP3R-SOCCs in Cr(vi)-induced cytosolic Ca(2+) overload and apoptosis in L-02 hepatocytes. Toxicol Res (Camb) 7(3):521–528. https://doi.org/10.1039/c8tx00029h

    Article  CAS  Google Scholar 

  11. Huang C, Jiao H, Song Z, Zhao J, Wang X, Lin H (2015) Heat stress impairs mitochondria functions and induces oxidative injury in broiler chickens. J Anim Sci 93(5):2144–2153. https://doi.org/10.2527/jas.2014-8739

    Article  CAS  PubMed  Google Scholar 

  12. Song Z, Zhao T, Liu L, Jiao H, Lin H (2011) Effect of copper on antioxidant ability and nutrient metabolism in broiler chickens stimulated by lipopolysaccharides. Arch Anim Nutr 65(5):366–375. https://doi.org/10.1080/1745039x.2011.609753

    Article  CAS  PubMed  Google Scholar 

  13. Barhoma RAE (2019) The role of eugenol in the prevention of chromium-induced acute kidney injury in male albino rats. Alexandria J Med 54(4):711–715. https://doi.org/10.1016/j.ajme.2018.05.006

    Article  Google Scholar 

  14. Figgitt M, Newson R, Leslie IJ, Fisher J, Ingham E, Case CP (2010) The genotoxicity of physiological concentrations of chromium (Cr(III) and Cr(VI)) and cobalt (Co(II)): an in vitro study. Mutat Res 688(1–2):53–61. https://doi.org/10.1016/j.mrfmmm.2010.03.008

    Article  CAS  PubMed  Google Scholar 

  15. 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(2):151-159. https://doi.org/10.1136/oemed-2014-102178

  16. Wang Y, Liu Y, Wan H, Zhu Y, Chen P, Hao P, Cheng Z, Liu J (2017) Moderate selenium dosing inhibited chromium (VI) toxicity in chicken liver. J Biochem Mol Toxicol 31(8). https://doi.org/10.1002/jbt.21916

  17. De Flora S, Camoirano A, Bagnasco M, Bennicelli C, Corbett GE, Kerger BD (1997) Estimates of the chromium(VI) reducing capacity in human body compartments as a mechanism for attenuating its potential toxicity and carcinogenicity. Carcinogenesis 18(3):531–537. https://doi.org/10.1093/carcin/18.3.531

    Article  PubMed  Google Scholar 

  18. Wan H, Zhu Y, Chen P, Wang Y, Hao P, Cheng Z, Liu Y, Liu J (2017) Effect of various selenium doses on chromium(IV)-induced nephrotoxicity in a male chicken model. Chemosphere 174:306–314. https://doi.org/10.1016/j.chemosphere.2017.01.143

    Article  CAS  Google Scholar 

  19. Ceriello A, Assaloni R, Da Ros R, Maier A, Piconi L, Quagliaro L, Esposito K, Giugliano D (2005) Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 111(19):2518–2524. https://doi.org/10.1161/01.Cir.0000165070.46111.9f

    Article  CAS  PubMed  Google Scholar 

  20. Shi JX, Wang QJ, Li H, Huang Q (2016) Silencing of USP22 suppresses high glucose-induced apoptosis, ROS production and inflammation in podocytes. Mol BioSyst 12(5):1445–1456. https://doi.org/10.1039/c5mb00722d

    Article  CAS  PubMed  Google Scholar 

  21. Sridharan S, Jain K, Basu A (2011) Regulation of autophagy by kinases. Cancers (Basel) 3(2):2630–2654. https://doi.org/10.3390/cancers3022630

    Article  CAS  Google Scholar 

  22. Wu D, Luo N, Wang L, Zhao Z, Bu H, Xu G, Yan Y, Che X, Jiao Z, Zhao T, Chen J, Ji A, Li Y, Lee GD (2017) Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS/MAPK and NF-kappaB signaling pathways. Sci Rep 7(1):455. https://doi.org/10.1038/s41598-017-00557-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang G, Chang CC, Yang Y, Yuan L, Xu L, Ho CT, Li S (2018) Resveratrol alleviates rheumatoid arthritis via reducing ROS and inflammation, inhibiting MAPK signaling pathways, and suppressing angiogenesis. J Agric Food Chem 66(49):12953–12960. https://doi.org/10.1021/acs.jafc.8b05047

    Article  CAS  PubMed  Google Scholar 

  24. Niu Y, Sun Q, Zhang G, Liu X, Shang Y, Xiao Y, Liu S (2018) Fowl adenovirus serotype 4-induced apoptosis, autophagy, and a severe inflammatory response in liver. Vet Microbiol 223:34–41. https://doi.org/10.1016/j.vetmic.2018.07.014

    Article  CAS  PubMed  Google Scholar 

  25. Jin Y, Liu Z, Liu F, Ye Y, Peng T, Fu Z (2015) Embryonic exposure to cadmium (II) and chromium (VI) induce behavioral alterations, oxidative stress and immunotoxicity in zebrafish (Danio rerio). Neurotoxicol Teratol 48:9–17. https://doi.org/10.1016/j.ntt.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  26. al-Harbi MM, Osman AM, al-Gharably NM, al-Bekairi AM, al-Shabanah OA, Sabah DM, Raza M (1995) Effect of desferrioxamine on cisplatin-induced nephrotoxicity in normal rats. Chemotherapy 41(6):448–454. https://doi.org/10.1159/000239381

    Article  CAS  PubMed  Google Scholar 

  27. 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(29):30444–30451. https://doi.org/10.1007/s11356-019-06253-0

    Article  CAS  PubMed  Google Scholar 

  28. Molina-Jijon E, Zarco-Marquez G, Medina-Campos ON, Zatarain-Barron ZL, Hernandez-Pando R, Pinzon E, Zavaleta RM, Tapia E, Pedraza-Chaverri J (2012) Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: role of Cr(VI) chelation. Toxicology 291(1–3):93–101. https://doi.org/10.1016/j.tox.2011.11.003

    Article  CAS  PubMed  Google Scholar 

  29. Dai H, Deng Y, Zhang J, Han H, Zhao M, Li Y, Zhang C, Tian J, Bing G, Zhao L (2015) PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells. Toxicology 334:72–80. https://doi.org/10.1016/j.tox.2015.06.003

    Article  CAS  PubMed  Google Scholar 

  30. Gao F, Chen D, Si J, Hu Q, Qin Z, Fang M, Wang G (2015) The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum Mol Genet 24(9):2528–2538. https://doi.org/10.1093/hmg/ddv017

    Article  CAS  PubMed  Google Scholar 

  31. Zhang HT, Mi L, Wang T, Yuan L, Li XH, Dong LS, Zhao P, Fu JL, Yao BY, Zhou ZC (2016) PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells. Toxicol in Vitro 34:212–219. https://doi.org/10.1016/j.tiv.2016.04.006

    Article  CAS  PubMed  Google Scholar 

  32. Yin F, Yan J, Zhao Y, Guo KJ, Zhang ZL, Li AP, Meng CY, Guo L (2019) Bone marrow mesenchymal stem cells repair Cr (VI)- injured kidney by regulating mitochondria-mediated apoptosis and mitophagy mediated via the MAPK signaling pathway. Ecotoxicol Environ Saf 176:234–241. https://doi.org/10.1016/j.ecoenv.2019.03.093

    Article  CAS  PubMed  Google Scholar 

  33. Eiyama A, Okamoto K (2015) PINK1/Parkin-mediated mitophagy in mammalian cells. Curr Opin Cell Biol 33:95–101. https://doi.org/10.1016/j.ceb.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  34. Fujimaki M, Saiki S, Sasazawa Y, Ishikawa KI, Imamichi Y, Sumiyoshi K, Hattori N (2018) Immunocytochemical monitoring of PINK1/Parkin-mediated mitophagy in cultured cells. Methods Mol Biol 1759:19–27. https://doi.org/10.1007/7651_2017_20

    Article  CAS  PubMed  Google Scholar 

  35. Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12(2):119–131. https://doi.org/10.1038/ncb2012

    Article  CAS  PubMed  Google Scholar 

  36. 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(5):986–997. https://doi.org/10.1002/ijc.30789

    Article  CAS  PubMed  Google Scholar 

  37. Huang C, Andres AM, Ratliff EP, Hernandez G, Lee P, Gottlieb RA (2011) Preconditioning involves selective mitophagy mediated by Parkin and p62/SQSTM1. PLoS One 6(6):e20975. https://doi.org/10.1371/journal.pone.0020975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Strappazzon F, Nazio F, Corrado M, Cianfanelli V, Romagnoli A, Fimia GM, Campello S, Nardacci R, Piacentini M, Campanella M, Cecconi F (2015) AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ 22(3):517. https://doi.org/10.1038/cdd.2014.190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kawajiri S, Saiki S, Sato S, Sato F, Hatano T, Eguchi H, Hattori N (2010) PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy. FEBS Lett 584(6):1073–1079. https://doi.org/10.1016/j.febslet.2010.02.016

    Article  CAS  PubMed  Google Scholar 

  40. Lan R, Wu JT, Wu T, Ma YZ, Wang BQ, Zheng HZ, Li YN, Wang Y, Gu CQ, Zhang Y (2018) Mitophagy is activated in brain damage induced by cerebral ischemia and reperfusion via the PINK1/Parkin/p62 signalling pathway. Brain Res Bull 142:63–77. https://doi.org/10.1016/j.brainresbull.2018.06.018

    Article  CAS  PubMed  Google Scholar 

  41. Zha Z, Wang J, Wang X, Lu M, Guo Y (2017) Involvement of PINK1/Parkin-mediated mitophagy in AGE-induced cardiomyocyte aging. Int J Cardiol 227:201–208. https://doi.org/10.1016/j.ijcard.2016.11.161

    Article  PubMed  Google Scholar 

  42. Wu L, Maimaitirexiati X, Jiang Y, Liu L (2016) Parkin regulates mitochondrial autophagy after myocardial infarction in rats. Med Sci Monit 22:1553–1559. https://doi.org/10.12659/msm.898722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The project was supported by the National Nature Science Foundation of China (No. 31872535), Shandong Natural Science Foundation of China (ZR2018MC027), Shandong Key R&D Program (GG201809160113), China Postdoctoral Science Foundation (2018M632704, 2019T120601), and Funds of Shandong “Double Tops” Program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jianzhu Liu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Wang, X., Wang, L. et al. Mitophagy Induced by Mitochondrial Function Damage in Chicken Kidney Exposed to Cr(VI). Biol Trace Elem Res 199, 703–711 (2021). https://doi.org/10.1007/s12011-020-02176-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02176-x

Keywords

Navigation