Skip to main content
Log in

Molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in multiple myeloma: a pilot study

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

This study explored the molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in human multiple myeloma cell line RPMI8226 cells. RT-PCR and qRT-PCR were used to evaluate the transcriptional levels of Deptor, JNK1, JNK2, JNK3, Raf-1, p53, p21 and NFκB1 at 0, 6, 12, 18, 24 and 48 h after nutrient depletion in RPMI8226 cells. We found that transcriptional levels of Deptor were increased time-dependently at 0, 6, 12 and 18 h, and then decreased. Its alternation was consistent with autophagy. Transcriptional levels of Raf-1, JNK1, JNK2, p53 and p21 were increased time-dependently at 0, 6, 12, 18, 24 and 48 h accompanying with the increase of apoptosis. Transcriptional levels of NFκB1 at 6, 12, 18, 24 and 48 h were decreased as compared with 0 h. It was suggested that all the studied signaling molecules were involved in cellular response to nutrient depletion in RPMI8226 cells. Deptor contributed to autophagy in this process. Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFκB1 may play a possible role in inhibiting apoptosis. It remained to be studied whether Deptor was involved in both autophagy and apoptosis.

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.

Similar content being viewed by others

References

  1. Peterson TR, Laplante M, Thoreen CC, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell, 2009,137(5):873–886

    Article  PubMed  CAS  Google Scholar 

  2. Schaeffer HJ, Weber MJ. Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol, 1999,19(4):2435–2444

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Nishina H, Vaz C, Billia P, et al. Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4. Development, 1999, 126(3):505–516

    PubMed  CAS  Google Scholar 

  5. Ogata M, Hino S, Saito A, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol, 2006,26(24):9220–9231

    Article  PubMed  CAS  Google Scholar 

  6. Wei Y, Pattingre S, Sinha S, et al. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Autophagy, 2008,30(5):678–688

    CAS  Google Scholar 

  7. Howe LR, Leevers SJ, Gomez N, et al. Activation of the MAP kinase pathway by the protein kinase raf. Cell, 1992,71(2):335–341

    Article  PubMed  CAS  Google Scholar 

  8. Chang L, Karin M. Mammalian MAP kinase signaling cascades. Nature, 2001,410(6824):37–40

    Article  PubMed  CAS  Google Scholar 

  9. Schireiber M, Kolbus A, Piu F, et al. Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev, 1999,13(5):607–619

    Article  Google Scholar 

  10. Vogelstein B, Lane D, Levine AJ, et al. Surfing the p53 network. Nature, 2000,408(6810):307–310

    Article  PubMed  CAS  Google Scholar 

  11. Deiry WS, Harper JW, Connor PM, et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res, 1994,54(5):1169–1174

    PubMed  Google Scholar 

  12. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell, 1995,80(2):293–299

    Article  PubMed  CAS  Google Scholar 

  13. Kucharczak J, Simmons MJ, Fan Y, et al. To be, or not to be: NF-κB is the answer — role of Rel/NF-κB in the regulation of apoptosis. Oncogene, 2003,22(56):8961–8982

    Article  PubMed  CAS  Google Scholar 

  14. Gilmore TD. The Rel1/NF-κB/IκB signal transduction pathway and cancer. Cancer Treat Res, 2003,115:241–265

    Article  PubMed  CAS  Google Scholar 

  15. Karin M, Lin A. NF-κB at the crossroads of life and death. Nat Immunol, 2002,3(3):221–227

    Article  PubMed  CAS  Google Scholar 

  16. Hoffmann A, Leung TH, Baltimore D et al. Genetic analysis of NF-κB/Rel transcription factors defines functional specificities. EMBO, 2003,22(20):5530–5539

    Article  CAS  Google Scholar 

  17. Carracedo A, Ma L, Teruya-Feldstein J, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest, 2008,118(9):3065–3074

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene, 2008,27(22):6245–6251

    Article  PubMed  CAS  Google Scholar 

  20. Tournier C, Hess P, Yang DD, et al. Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science, 2000,288(5467):870–874

    Article  PubMed  CAS  Google Scholar 

  21. Chipuk JE, Kuwana T, Bouchier-Hayes L, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 2004, 303(5660):1010–1014

    Article  PubMed  CAS  Google Scholar 

  22. Bost F, McKay R, Bost M, et al. The Jun kianse 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells. Mol Cell Biol, 1999,19(3):1938–1949

    PubMed  CAS  Google Scholar 

  23. Potapova O, Anisimov SV, Gorospe M, et al. Targets of c-Jun NH(2)-terminal kinase 2-mediated tumor growth regulation revealed by serial analysis of gene expression. Cancer Res, 2002,62(11):3257–3263

    PubMed  CAS  Google Scholar 

  24. Potapova O, Gorospe M, Dougherty RH, et al. Inhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p53-dependent manner. Mol Cell Biol, 2000,20(5):1713–1722

    Article  PubMed  CAS  Google Scholar 

  25. Wu H, Wang MC, Bohmann D. JNK protects Drosophila from oxidative stress by trancriptionally activating autophagy. Mech Dev, 2009,126(8–9):624–637

    Article  PubMed  CAS  Google Scholar 

  26. Salminen A, Kaarniranta K. Regulation of the aging process by autophagy. Trends Mol Med, 2009,15(5):217–224

    Article  PubMed  CAS  Google Scholar 

  27. Zhang Y, Wu Y, Wu D, et al. NF-κB facilitates oridonin-induced apoptosis and autophagy in HT1080 cells through a p53-mediated pathway. Arch Biochem Biophys, 2009,489(1–2):25–33

    Article  PubMed  CAS  Google Scholar 

  28. Papa S, Zazzeroni F, Pham CG, et al. Linking JNK signaling to NF-κB: a key to survival. J Cell Sci, 2004,117(Pt22):5197–5208

    Article  PubMed  CAS  Google Scholar 

  29. Nakano H, Nakajima A, Sakon-Komazawa S, et al. Reactive oxygen species mediate crosstalk between NF-κB and JNK. Cell Death Different, 2006,13(5):730–737

    Article  CAS  Google Scholar 

  30. Liu J, Lin A. Role of JNK activation in apoptosis: A double-edged sword. Cell Res, 2005,15(1):36–42

    Article  PubMed  Google Scholar 

  31. Bubici C, Papa S, Pham CG, et al. NF-κB and JNK. Cell Cycle, 2004,3(12):1524–1529

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guohui Cui  (崔国惠).

Additional information

The authors contributed equally to this work.

This project was supported by a grant from National Natural Science Foundation of China (No. 30871036).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Y., Chen, Y., Wen, L. et al. Molecular mechanisms underlying the time-dependent autophagy and apoptosis induced by nutrient depletion in multiple myeloma: a pilot study. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 32, 1–8 (2012). https://doi.org/10.1007/s11596-012-0001-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-012-0001-2

Key words

Navigation