Skip to main content
SpringerLink
Log in

Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Many studies have demonstrated that oxidative stress-induced apoptosis is a main cause of follicular atresia. Reactive oxygen species (ROS)-induced granulosa cell (GC) apoptosis is regulated by a variety of signaling pathways involving numerous genes and transcription factors. In this study, we found expression of the p53-upregulated modulator of apoptosis (PUMA), a BH3-only Bcl-2 subfamily protein, in ovarian GCs during oxidative stress. By overexpression and knockdown of Forkhead box O1 (FoxO1), we found that FoxO1 regulates PUMA at the protein level. Moreover, as c-Jun N-terminal kinase (JNK) has been shown to activate FoxO1 by promoting its nuclear import, we used a JNK inhibitor to reduce FoxO1 activation and detected decreased PUMA messenger RNA expression and protein levels during oxidative stress. In addition, in vivo oxidative stress-induced upregulation of PUMA was found following injection of 3 nitropropionic acid in mice. In conclusion, oxidative stress increases PUMA expression regulated by FoxO1 in follicular GCs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2000;5(5):415–418.

    Article  CAS  PubMed  Google Scholar 

  2. Asselin E, Xiao CW, Wang YF, Tsang BK. Mammalian follicular development and atresia: role of apoptosis. Biol Signals Recept. 2000;9(2):87–95.

    Article  CAS  PubMed  Google Scholar 

  3. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407(6805):770–776.

    Article  CAS  PubMed  Google Scholar 

  4. Green DR, Evan GI. A matter of life and death. Cancer Cell. 2002;1(1):19–30.

    Article  CAS  PubMed  Google Scholar 

  5. Hsu SY, Hsueh AJ. Tissue-specific Bc1-2 protein partners in apoptosis: An ovarian paradigm. Physiol Rev. 2000;80(2): 593–614.

    Article  CAS  PubMed  Google Scholar 

  6. Johnson AL, Bridgham JT, Jensen T. Bc1-X(LONG) protein expression and phosphorylation in granulosa cells. Endocrinology. 1999;140(10):4521–4529.

    Article  CAS  PubMed  Google Scholar 

  7. Ming L, Wang P, Bank A, Yu J, Zhang L. PUMA Dissociates Bax and Bcl-X(L) to induce apoptosis in colon cancer cells. J Biol Chem. 2006;281(23):16034–16042.

    Article  CAS  PubMed  Google Scholar 

  8. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408(6809):239–247.

    Article  CAS  PubMed  Google Scholar 

  9. Ki YW, Park JH, Lee JE, Shin IC, Koh HC. JNK and p38 MAPK regulate oxidative stress and the inflammatory response in chlorpyrifos-induced apoptosis. Toxicol Lett. 2013;218(3): 235–245.

    Article  CAS  PubMed  Google Scholar 

  10. Shen M, Lin F, Zhang J, Tang Y, Chen WK, Liu H. Involvement of the up-regulated FoxO1 expression in follicular granulosa cell apoptosis induced by oxidative stress. J Biol Chem. 2012;287(31): 25727–25740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Steckley D, Karajgikar M, Dale LB, et al. Puma is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J Neurosci. 2007;27(47):12989–12999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dudgeon C, Wang P, Sun X, et al. PUMA induction by FoxO3a mediates the anticancer activities of the broad-range kinase inhibitor UCN-01. Mol Cancer Ther. 2010;9(11): 2893–2902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hikisz P, Kilianska ZM. PUMA, a critical mediator of cell death–one decade on from its discovery. Cell Mol Biol Lett. 2012;17(4):646–669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shen B, Chao L, Chao J. Pivotal role of JNK-dependent FOXO1 activation in downregulation of kallistatin expression by oxidative stress. Am J Physiol Heart Circ Physiol. 2010;298(3): H1048–H1054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Montilla P, Tunez I, Munoz MC, et al. Effect of glucocorticoids on 3-nitropropionic acid-induced oxidative stress in synaptosomes. Eur J Pharmacol. 2004;488(1–3):19–25.

    Article  CAS  PubMed  Google Scholar 

  16. Wang XL, Wu Y, Tan LB, et al. Follicle-stimulating hormone regulates pro-apoptotic protein Bcl-2-interacting mediator of cell death-extra long (BimEL)-induced porcine granulosa cell apoptosis. J Biol Chem. 2012;287(13):10166–10177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bennett BL, Sasaki DT, Murray BW, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci. 2001;98(24):13681–13686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3:28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Wu Y, Wang XL, Liu JH, et al. BIM EL-mediated apoptosis in cumulus cells contributes to degenerative changes in aged porcine oocytes via a paracrine action. Theriogenology. 2011;76(8):1487–1495.

    Article  CAS  PubMed  Google Scholar 

  20. Wu B, Qiu W, Wang P, et al. p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia-reperfusion. Gut. 2007;56(5):645–654.

    Article  CAS  PubMed  Google Scholar 

  21. Bean GR, Ganesan YT, Dong Y, et al. PUMA and BIM are required for oncogene inactivation-induced apoptosis. Sci Signal. 2013;6(268):ra20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. You H, Pellegrini M, Tsuchihara K, et al. FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal. J Exp Med. 2006;203(7):1657–1663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang JQ, Shen M, Zhu CC, et al. 3-nitropropionic Acid induces ovarian oxidative stress and impairs follicle in mouse. PloS One. 2014;9(2):e86589.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Murdoch WJ. Inhibition by oestradiol of oxidative stress-induced apoptosis in pig ovarian tissues. J Reprod fertil. 1998;114(1): 127–130.

    Article  CAS  PubMed  Google Scholar 

  25. Dey P, Strom A, Gustafsson JA. Estrogen receptor beta upregulates FOXO3a and causes induction of apoptosis through PUMA in prostate cancer. Oncogene. 2014;33(33):4213–4225.

    Article  CAS  PubMed  Google Scholar 

  26. Essers MA, Weijzen S, de Vries-Smits AM, et al. FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. EMBO J. 2004;23(24): 4802–4812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Modur V, Nagarajan R, Evers BM, Milbrandt J. FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem. 2002;277(49):47928–47937.

    Article  CAS  PubMed  Google Scholar 

  28. Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96(6):857–868.

    Article  CAS  PubMed  Google Scholar 

  29. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103(2):239–252.

    Article  CAS  PubMed  Google Scholar 

  30. Waetzig V, Herdegen T. Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage. Trends Pharmacol Sci. 2005;26(9):455–461.

    CAS  PubMed  Google Scholar 

  31. Bode AM, Dong Z. The Functional Contrariety of JNK. Mol Carcinog. 2007;46(8):591–598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sunayama J, Tsuruta F, Masuyama N, Gotoh Y. JNK antagonizes Akt-mediated survival signals by phosphorylating 14-3-3. J Cell Biol. 2005;170(2):295–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhao X, Gan L, Pan H, et al. Multiple elements regulate nuclear/ cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms. Biochem J. 2004;378(pt 3):839–849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Essaghir A, Dif N, Marbehant CY, Coffer PJ, Demoulin JB. The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors. J Biol Chem. 2009;284(16): 10334–10342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhou J, Liao W, Yang J, et al. FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway. Autophagy. 2012;8(12):1712–1723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Oleinik NV, Krupenko NI, Krupenko SA. Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007;26(51):7222–7230.

    Article  CAS  PubMed  Google Scholar 

  37. Jin M, Ande A, Kumar A, Kumar S. Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc/jnk/sp1 pathway. Cell Death Dis. 2013;4:e554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cazanave SC, Mott JL, Elmi NA, et al. JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis. J Biol Chem. 2009;284(39):26591–2602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhao Z, Wang J, Tang J, et al. JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant ovarian cancer cells. Biochem J. 2012;444(2):291–301.

    Article  CAS  PubMed  Google Scholar 

  40. Fan S, Qi M, Yu Y, et al. P53 activation plays a crucial role in silibinin induced ROS generation via PUMA and JNK. Free Radic Res. 2012;46(3):310–319.

    Article  CAS  PubMed  Google Scholar 

  41. Ming L, Sakaida T, Yue W, Jha A, Zhang L, Yu J. Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis. 2008;29(10):1878–1884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Barthélémy C, Henderson CE, Pettmann B. Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK. BMC Neurosci. 2004;5(1):48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, PR China

    Ze-Qun Liu MSc, Ming Shen PhD, Wang-Jun Wu PhD, Bo-Jiang Li MSc, Qian-Nan Weng BS, Mei Li PhD & Hong-Lin Liu PhD

Authors
  1. Ze-Qun Liu MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming Shen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wang-Jun Wu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo-Jiang Li MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qian-Nan Weng BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mei Li PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong-Lin Liu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mei Li PhD or Hong-Lin Liu PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, ZQ., Shen, M., Wu, WJ. et al. Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress. Reprod. Sci. 22, 696–705 (2015). https://doi.org/10.1177/1933719114556483

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719114556483

Keywords

Search

Navigation