Skip to main content
SpringerLink
Log in

ER stress-induced caspase-12 activation is inhibited by PKC in neuronal cells

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Caspase-12 is activated when the cells are exposed to excess levels of various stimuli, which cause endoplasmic reticulum (ER) stress. Protein kinase C (PKC) plays an important role in many signaling pathways in cells, and the activation of PKC has multiple actions in the signaling function of the ER. This study examined whether or not phorbol 12, 13-dibutyrate (PDBu)-induced PKC activation modulates caspase-12 cleavage and it’s processing, using a wild type caspase-12 overexpressing neuronal cell line, known as Cas-12 cells. The thapsigargin treatment induced caspase-12 fragmentation in the Cas-12 cells. This was inhibited by PKC, which had previously been stimulated by PDBu. The PDBu treatment attenuated the ER stress-induced translocation of caspase-12 from the ER to the cytoplasm. The caspase-3 specific inhibitor blocked caspase-12 fragmentation, and purified caspase-12 was cleaved by the active caspase-3 in vitro, suggesting thatcaspase-12 might be a substrate for caspase-3. In addition, the PDBu treatment influenced the decrease of active caspase-3 fragment. These results suggest that an ER stress induces the activation of caspase-12 via caspase-3, and that PKC regulates both caspase-12 and caspase-3 activations in Cas-12 cells

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. Salvesen GS, Dixit VM. Caspases: Intracellular signaling by proteolysis. Cell 1997; 91: 443–446

    CAS  PubMed  Google Scholar 

  2. Thornberry NA, Lazebnik Y. Caspases: Enemies within. Science 1998; 281: 1312–1316

    CAS  PubMed  Google Scholar 

  3. Zheng TS, Flavell RA. Apoptosis. All’s well that ends dead. Nature 1999; 400: 410–411

    CAS  PubMed  Google Scholar 

  4. Van de Craen M, Vandenabeele P, Declercq W, et al. Characterization of seven murine caspase family members. FEBS Lett 1997; 403: 61–69

    CAS  PubMed  Google Scholar 

  5. Hu S, Snipas SJ, Vincenz C, et al. Caspase-14 is a novel developmentally regulated protease. J Biol Chem 1998; 273: 29648–29653

    CAS  PubMed  Google Scholar 

  6. Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000; 403: 98–103

    CAS  PubMed  Google Scholar 

  7. Nakagawa T, Yuan J. Cross-talk between two cystein protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 2000; 150: 887–894

    Article  CAS  PubMed  Google Scholar 

  8. Gervais FG, Xu D, Robertson GS, et al. Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid- beta precursor protein and amyloidogenic A beta peptide formation. Cell 1999; 97: 395–406

    CAS  PubMed  Google Scholar 

  9. Wootz H, Hansson I, Korhonen L, et al. Caspase-12 cleavage and increased oxidative stress during motor neuron degeneration in transgenic mouse model of ALS. Biochem Biophys Res Commun 2004; 322(1): 281–286

    CAS  PubMed  Google Scholar 

  10. Bitko V, Barik S. An endoplasmic reticulum-specific stress-activated caspase (caspase-12) is implicated in the apoptosis of A549 epithelial cells by respiratory syncytial virus. J Cell Biochem 2001; 80: 441–454

    CAS  PubMed  Google Scholar 

  11. Rao RV, Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem 2001; 276: 33869–33874

    CAS  PubMed  Google Scholar 

  12. Gómez-Angelats M, Bortner CD, Cidlowski JA. Protein kinase C (PKC) inhibits Fas receptor-induced apoptosis through modulation of the loss of K+ and cell shrinkage. A role for PKC upstream of caspases. J Biol Chem 2000; 275: 19609–19619

    PubMed  Google Scholar 

  13. Gómez-Angelats M, Cidlowski JA. Protein kinase C regulates FADD recruitment and death-inducing signaling complex formation in Fas/CD95-induced apoptosis. J Biol Chem 2001; 276: 44944–44952

    PubMed  Google Scholar 

  14. Stennicke HR, Deveraux QL, Humke EW, et al. Caspase-9 can be activated without proteolytic processing. J Biol Chem 1999; 274: 8359–8362

    CAS  PubMed  Google Scholar 

  15. Xia Z, Kam CM, Huang C, et al. Expression and purification of enzymatically active recombinant granzyme B in a baculovirus system. Biochem Biophys Res Commun 1998; 243: 384–389

    CAS  PubMed  Google Scholar 

  16. Liu X, Zou H, Widlak P, Garrard W, Wang X. Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1. J Biol Chem 1999; 274: 13836–13840

    CAS  PubMed  Google Scholar 

  17. Pedrosa Ribeiro CM, McKay RR, Hosoki E, et al. Effects of elevated cytoplasmic calcium and protein kinase C on endoplasmic reticulum structure and function in HEK293 cells. Cell Calcium 2000; 27: 175–85

    CAS  PubMed  Google Scholar 

  18. Cryns V, Yuan J. Proteases to die for. Genes Dev 1998; 12: 1551–1570

    CAS  PubMed  Google Scholar 

  19. Fernandes-Alnemri T, Takahashi A, Armstrong R, et al. Mch3, a novel human apoptotic cystein protease highly related to CPP32. Cancer Res 1995; 55: 6045–52

    CAS  PubMed  Google Scholar 

  20. Welihinda AA, Tirasophon W, Kaufman RJ. The cellular response to protein misfolding in the endoplasmic reticulum. Gene Expr 1999; 7: 293–300

    CAS  PubMed  Google Scholar 

  21. Tan Y, Ruan H, Demeter MR, Comb MJ. p90 (RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway. J Biol Chem 1999; 274: 34859–34867

    CAS  PubMed  Google Scholar 

  22. Whitman SP, Civoli F, Daniel LW. Protein kinase CbetaII activation by 1-beta-D-arabinofuranosylcytosine is antagonistic to stimulation of apoptosis and Bcl-2alpha down-regulation. J Biol Chem 1997; 272: 23481–23484

    CAS  PubMed  Google Scholar 

  23. Mizuno K, Noda K, Araki T, et al. The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, correlates with Fas-mediated and 12-O-tetradecanoyl-phorbol-13-acetate-induced apoptosis. Eur J Biochem 1997; 250: 7–18

    CAS  PubMed  Google Scholar 

  24. Ruiz-Ruiz MC, Izquierdo M, de Murcia G, Lopez-Rivas A. Activation of protein kinase C attenuates early signals in Fas-mediated apoptosis. Eur J Immunol 1997; 27: 1442–1450

    CAS  PubMed  Google Scholar 

  25. Zhuang S, Demirs JT, Kochevar IE. Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation. Oncogene 2001; 20: 6764–6776

    CAS  PubMed  Google Scholar 

  26. Nicholson DW, Thornberry NA. Caspases: killer proteases. Trends Biochem Sci 1997; 22: 299–306

    CAS  PubMed  Google Scholar 

  27. Jayanthi S, Deng X, Noailles PA, et al. Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 2004; 18(2): 238–51

    CAS  PubMed  Google Scholar 

  28. Hitomi J, Katayama T, Taniguchi M, et al. Apoptosis induced by endoplasmic reticulum stress depends on activation of caspase-3 via caspase-12. Neurosci Lett 2004; 357(2): 127–130

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Korea

    J. H. Boo & I. Mook-Jung Ph.D.

  2. Department of Bio-Materials Engineering, Chosun University, Gwangju, Korea

    I.-S. Park Ph.D.

  3. Biomedical Research Center, The Functional Proteomics Center, Korea

    W. Lee & D. H. Kim

  4. Korea Institute of Science and Technology, Seoul, Korea

    W. Lee

  5. Digitalbiotech Inc., Ansan, Korea

    Y. H. Kim

  6. Department of Biochemistry, Seoul National University College of Medicine, Seoul, 110-799, Korea

    I. Mook-Jung Ph.D.

  7. Research Center for Proteineous Materials and Department of Bio-Materials Engineering, Chosun University, Gwangju, 501-759, Korea

    I.-S. Park Ph.D.

Authors
  1. W. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. H. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. H. Boo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. H. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I.-S. Park Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I. Mook-Jung Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Mook-Jung Ph.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, W., Kim, D.H., Boo, J.H. et al. ER stress-induced caspase-12 activation is inhibited by PKC in neuronal cells. Apoptosis 10, 407–415 (2005). https://doi.org/10.1007/s10495-005-0814-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-005-0814-6

Keywords

Search

Navigation