Skip to main content
Log in

Autophagy Protects MC3T3-E1 Cells upon Aluminum-Induced Apoptosis

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

Abstract

Aluminum (Al) exposure has adverse effects on osteoblasts, and the effect might be through autophagy-associated apoptosis. In this study, we showed that aluminum trichloride (AlCl3) could induce autophagy in MC3T3-E1 cells, as demonstrated by monodansylcadaverine (MDC) staining and the expressions of the ATG3, ATG5, and ATG9 genes. We found AlCl3 inhibited MC3T3-E1 cell survival rate and caused apoptosis, as evidenced by CCK-8 assay, Annexin V/PI double staining, and increased expressions of Bcl-2, Bax, and Caspase-3 genes. In addition, increased autophagy induced by rapamycin further attenuated the MC3T3-E1 cell apoptosis rate after AlCl3 exposure. These results support the hypothesis that autophagy plays a protective role in impeding apoptosis caused by AlCl3. Activating autophagy may be a strategy for treatment of Al-induced bone disease.

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

Similar content being viewed by others

References

  1. Yang X, Huo H, Xiu C, Song M, Han Y, Li Y, Zhu Y (2016) Inhibition of osteoblast differentiation by aluminum trichloride exposure is associated with inhibition of BMP-2/Smad pathway component expression. Food Chem Toxicol 97:120–126

    Article  PubMed  CAS  Google Scholar 

  2. Exley C (2013) Human exposure to aluminium. Environ Sci Process Impacts 15:1807–1816

    Article  PubMed  CAS  Google Scholar 

  3. Exley C (2014) Why industry propaganda and political interference cannot disguise the inevitable role played by human exposure to aluminum in neurodegenerative diseases, including Alzheimer’s disease. Front Neurol 5:212

    Article  PubMed  PubMed Central  Google Scholar 

  4. Vanduyn N, Settivari R, Levora J, Zhou S, Unrine J, Nass R (2013) The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration. J Neurochem 124:147–157

    Article  PubMed  CAS  Google Scholar 

  5. Crisponi G, Nurchi VM, Faa G, Remelli M (2011) Human diseases related to aluminium overload. Monatshefte für Chemie - Chemical Monthly 142:331–340

    Article  CAS  Google Scholar 

  6. Sun X, Liu J, Zhuang C, Yang X, Han Y, Shao B, Song M, Li Y, Zhu Y (2016) Aluminum trichloride induces bone impairment through TGF-beta1/Smad signaling pathway. Toxicology 371:49–57

    Article  PubMed  CAS  Google Scholar 

  7. Manolagas SC, Parfitt AM (2010) What old means to bone. Trends Endocrinol Metab 21:369–374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Cao Z, Fu Y, Sun X, Zhang Q, Xu F, Li Y (2016) Aluminum trichloride inhibits osteoblastic differentiation through inactivation of Wnt/beta-catenin signaling pathway in rat osteoblasts. Environ Toxicol Pharmacol 42:198–204

    Article  PubMed  CAS  Google Scholar 

  9. Huang W, Wang P, Shen T, Hu C, Han Y, Song M, Bian Y, Li Y, Zhu Y (2017) Aluminum trichloride inhibited osteoblastic proliferation and downregulated the Wnt/beta-catenin pathway. Biol Trace Elem Res 177:323–330

    Article  PubMed  CAS  Google Scholar 

  10. Cao Z, Liu D, Zhang Q, Sun X, Li Y (2016) Aluminum chloride induces osteoblasts apoptosis via disrupting calcium homeostasis and activating ca(2+)/CaMKII signal pathway. Biol Trace Elem Res 169:247–253

    Article  PubMed  CAS  Google Scholar 

  11. Li X, Han Y, Guan Y, Zhang L, Bai C, Li Y (2012) Aluminum induces osteoblast apoptosis through the oxidative stress-mediated JNK signaling pathway. Biol Trace Elem Res 150:502–508

    Article  PubMed  CAS  Google Scholar 

  12. Orrenius S, Kaminskyy VO, Zhivotovsky B (2013) Autophagy in toxicology: cause or consequence? Annu Rev Pharmacol Toxicol 53:275–297

    Article  PubMed  CAS  Google Scholar 

  13. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741

    Article  PubMed  CAS  Google Scholar 

  14. Kroemer G, Levine B (2008) Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 9:1004–1010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Chatterjee S, Sarkar S, Bhattacharya S (2014) Toxic metals and autophagy. Chem Res Toxicol 27:1887–1900

    Article  PubMed  CAS  Google Scholar 

  16. Liu W, Dai N, Wang Y, Xu C, Zhao H, Xia P, Gu J, Liu X, Bian J, Yuan Y, Zhu J, Liu Z (2016) Role of autophagy in cadmium-induced apoptosis of primary rat osteoblasts. Sci Rep 6:20404

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Lv XH, Zhao DH, Cai SZ, Luo SY, You T, Xu BL, Chen K (2015) Autophagy plays a protective role in cell death of osteoblasts exposure to lead chloride. Toxicol Lett 239:131–140

    Article  PubMed  CAS  Google Scholar 

  18. Bartolome A, Lopez-Herradon A, Portal-Nunez S, Garcia-Aguilar A, Esbrit P, Benito M, Guillen C (2013) Autophagy impairment aggravates the inhibitory effects of high glucose on osteoblast viability and function. Biochem J 455:329–337

    Article  PubMed  CAS  Google Scholar 

  19. Zeng KW, Fu H, Liu GX, Wang XM (2012) Aluminum maltolate induces primary rat astrocyte apoptosis via overactivation of the class III PI3K/Beclin 1-dependent autophagy signal. Toxicol in Vitro 26:215–220

    Article  PubMed  CAS  Google Scholar 

  20. Zhang QL, Niu Q, Niu PY, Ji XL, Zhang C, Wang L (2010) Novel interventions targeting on apoptosis and necrosis induced by aluminum chloride in neuroblastoma cells. J Biol Regul Homeost Agents 24:137–148

    PubMed  Google Scholar 

  21. Zhang QL, Niu Q, Ji XL, Conti P, Boscolo P (2008) Is necroptosis a death pathway in aluminum-induced neuroblastoma cell demise? Int J Immunopathol Pharmacol 21:787–796

    Article  PubMed  CAS  Google Scholar 

  22. Zhang C, Lin J, Ge J, Wang LL, Li N, Sun XT, Cao HB, Li JL (2017) Selenium triggers Nrf2-mediated protection against cadmium-induced chicken hepatocyte autophagy and apoptosis. Toxicol in Vitro 44:349–356

    Article  PubMed  CAS  Google Scholar 

  23. Song Y, Li N, Gu J, Fu S, Peng Z, Zhao C, Zhang Y, Li X, Wang Z, Li X, Liu G (2016) Beta-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway. J Dairy Sci 99:9184–9198

    Article  PubMed  CAS  Google Scholar 

  24. Sun X, Yuan X, Chen L, Wang T, Wang Z, Sun G, Li X, Li X, Liu G (2017) Histamine induces bovine rumen epithelial cell inflammatory response via NF-kappaB pathway. Cell Physiol Biochem 42:1109–1119

    Article  PubMed  CAS  Google Scholar 

  25. Du X, Zhu Y, Peng Z, Cui Y, Zhang Q, Shi Z, Guan Y, Sha X, Shen T, Yang Y, Li X, Wang Z, Li X, Liu G (2018) High concentrations of fatty acids and β-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows. J Dairy Sci. https://doi.org/10.3168/jds.2017-13234

  26. Yang L, Meng H, Yang M (2016) Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species. J Mol Endocrinol 56:291–300

    Article  PubMed  CAS  Google Scholar 

  27. Xu F, Ren L, Song M, Shao B, Han Y, Cao Z, Li Y (2017) Fas- and mitochondria-mediated signaling pathway involved in osteoblast apoptosis induced by AlCl3. Biol Trace Elem Res. https://doi.org/10.1007/s12011-017-1176-y

  28. Yang Q, Li S, Fu Z, Lin B, Zhou Z, Wang Z, Hua Y, Cai Z (2017) Shikonin promotes adriamycin induced apoptosis by upregulating caspase3 and caspase8 in osteosarcoma. Mol Med Rep 16(2):1347–1352

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Liang M, Russell G, Hulley P (2008) Bim, Bak, and Bax regulate osteoblast survival. Journal of Bone & Mineral Research 23:610–620

    Article  CAS  Google Scholar 

  30. Nagase Y, Makiyama I (2009) Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts. J Biol Chem 284:36659–36669

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Du X, Shi Z, Peng Z, Zhao C, Zhang Y, Wang Z, Li X, Liu G, Li X (2017) Acetoacetate induces hepatocytes apoptosis by the ROS-mediated MAPKs pathway in ketotic cows. J Cell Physiol 232:3296–3308

    Article  PubMed  CAS  Google Scholar 

  32. Nedelsky NB, Todd PK, Taylor JP (2008) Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection. Biochim Biophys Acta 1782:691–699

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Zheng L, Wang W, Ni J, Mao X, Song D, Liu T, Wei J, Zhou H (2017) Role of autophagy in tumor necrosis factor-alpha-induced apoptosis of osteoblast cells. J Investig Med 65:1014–1020

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by a research grant from the National Natural Science Foundation of China (No. 31372496).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yanfei Li.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, X., Zhang, J., Ji, Q. et al. Autophagy Protects MC3T3-E1 Cells upon Aluminum-Induced Apoptosis. Biol Trace Elem Res 185, 433–439 (2018). https://doi.org/10.1007/s12011-018-1264-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-018-1264-7

Keywords

Navigation