Abstract
A recent review article by Jänne et al. (1) begins with, “The polyamines, putrescine, spermidine, and spermine, are organic cations shown to participate in a bewildering number of cellular reactions, yet their exact functions in intermediary metabolism and specific interactions with cellular components remain largely elusive.” As documented by Schipper et al. (2) in their article entitled “Involvement of polyamines in apoptosis. Facts and controversies: effectors or protectors?” apoptosis or programmed cell death certainly belongs on the list. As the title of the Schipper et al. review indicates, the role of polyamines in apoptosis is anything but clear. In most, but not all instances, ornithine decarboxylase (ODC) activity increased with the induction of apoptosis, but there was no clear cut change in polyamine levels as they increased, decreased, or stayed the same depending on the system (2). Most experiments examining the effect of blocking ODC with α-difluoromethylornithine (DFMO) reported protection from apoptosis, whereas a few found no effect (2). The effects of polyamine analogs on apoptosis were also variable (2).
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References
Jäne, J., Alhonen, L., Pietilä, M., and Keinänen, T. A. (2004) Genetic approaches to the cellular functions of polyamines in mammals. Eur. J. Biochem. 271, 877–894.
Schipper, R. G., Penning, L. C., and Verhofstad, A. A. J. (2000) Involvement of polyamines in apoptosis. Facts and controversies: effectors or protectors? Semin. Cancer Biol. 10, 55–68.
Quaroni, A., Wands, J., Trelstad, R. L., and Isselbacher, K. J. (1979) Epithelioid cell cultures from rat small intestine. J. Cell Biol. 80, 248–265.
McCormack, S. A., Viar, M. J., and Johnson, L. R. (1993) Polyamines are necessary for cell migration by a small intestinal crypt cell line. Am. J. Physiol. Gastrointest. Liver Physiol. 264, G367–G374.
Ziegler, U. and Groscurth, P. (2004) Morphological features of cell death. News Physiol. Sci. 19, 124–128.
Thornberry, N. A. and Lazebnik, Y. (1998) Caspases: enemies within. Science 281, 1312–1316.
Liu, X., Li, P., Widlak, P., et al. (1998) The 40 kDa subunit of DNA fragmentation factors induces DNA fragmentation and condensation during apoptosis. Proc. Natl. Acad. Sci. USA 95, 8461–8466.
Nicholson, D. W. and Thornberry, N. A. (2003) Life and death decisions. Science 299, 214–215.
Deveraux, Q. L., Leo, E., Steinnicke, H. R., Welsh, K., Salvesen, G. S., and Reed, J. C. (1999) Cleavage of human inhibitors of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J. 18, 5242–5251.
Wu, G., Chai, J., Suber, T. L., et al. (2000) Structural basis of IAP recognition of Smac/Diablo. Nature 408, 1008–1012.
Kelekar, A. and Thompson, C. B. (1998) Bcl-2 family proteins: the role of the BH3 domain in apoptosis. Trends Cell. Biol. 8, 324–330.
Oltvai, Z. N., Milliman, C. L., and Korsmeyer, S. J. (1993) Bcl-2 heterodimerizes with a conserved homolog, Bax, that accelerates programmed cell death. Cell in Vivo 74, 609–619.
Ledgerwood, E. C., Pober, J. S., and Bradley, J. R. (1999) Recent advances in the molecular basis of TNF signal transduction. Lab. Invest. 79, 1041–1050.
Hsu, H., Shu, H.-B., Pan, M.-G., and Goedeel, D. V. (1996) TRADD-TRF2 and TRADDFADD interaction define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299–309.
Beg, A. A. and Baltimore, D. (1996) An essential role for NF-κB in preventing TNF-α induced cell death. Science 274, 782–784.
Lewis, T. S., Shapiro, P. S., and Ahn, N. G. (1998) Signal transduction through MAPK cascades. Adv. Cancer Res. 74, 49–139.
Reinhard, C., Shamoon, B., Shyamala, V., and Williams, L. T. (1997) TNFα-induced activation of JNK is mediated by TRAF2. EMBO J. 16, 1080–1092.
Bhattacharya, S., Ray, R. M., and Johnson, L. R. (2004) Prevention of TNF-α-induced apoptosis in polyamine-depleted IEC-6 cells is mediated through the activation of ERK 1/2. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G479–G490.
Wright, N. A. and Irwin, M. (1982) The kinetics of villus cell populations in the mouse small intestine: normal villi-the steady state requirement. Cell Tissue Kinet. 15, 595–609.
Grossman, J., Walther, K., Artinger, M., Kiessling, S., and Scholmerich, J. (2001) Apoptotic signaling during initiation of detachment induced apoptosis (“anoikis”) of primary human intestinal epithelial cells. Cell Growth Differ. 12, 147–155.
Ray, R. M., Zimmerman, B. J., McCormack, S. A., Patel, T. B., and Johnson, L. R. (1999) Polyamine depletion arrests cell cycle and induces inhibitors p21waf1/cip1, p27kip1 and p53 in IEC-6 cells. Am. J. Physiol. Cell Physiol. 276, C684–C691.
Agarwal, M. L., Taylor, W. R., Chernov, M. V., Chernova, O. B., and Stark, G. R. (1998) The p53 network. J. Biol. Chem. 273, 1–4.
Merritt, A. J., Potten, C. S., Kemp, C. J., et al. (1994) The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res. 54, 614–617.
Ray, R. M., Viar, M. J., Yuan, Q., and Johnson, L. R. (2000) Polyamine depletion delays apoptosis of rat intestinal epithelial cells. Am. J. Physiol. Cell Physiol. 278, C480–C489.
Deng, W. and Johnson, L. R. (2005) Polyamine depletion inhibits irradiation-induced apoptosis in intestinal epithelia. Am. J. Physiol. Gastrointest. Liver Physiol. 289, G599–G606.
Yuan, Q., Ray, R. M., and Johnson, L. R. (2002) Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c. Am. J. Physiol. Cell Physiol. 282, C1290–C1297.
Bhattacharya, S., Ray, R. M., Viar, M. J., and Johnson, L. R. (2003) Polyamines are required for the activation of c-Jun NH2-terminal kinase and apoptosis in response to TNF-α in IEC-6 cells. Am. J. Physiol. Gstrointest. Liver Physiol. 285, G980–G991.
Pfeffer, L. M., Yang, C. H., Murti, A., et al. (2001) Polyamine depletion induces rapid NF-κB activation in IEC-6 cells. J. Biol. Chem. 276, 45,909–45,913.
Li, L., Rao, J. N., Bass, B. L., and Wang, J.-Y. (2001) NF-κB activation and susceptibility to apoptosis after polyamine depletion in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G992–G1004.
Zou, T., Rao, J. N., Guo, X., et al. (2004) NF-(kappa)B-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion. Am. J. Physiol. Cell Physiol. 286, C1009–C1018.
Madrid, L. V., Wang, C. Y., Guttridge, D. C., Schottelins, A. J., Baldwin, A. S. Jr., and Mayo, M. W. (2000) Akt suppresses apoptosis by stimulating the transactivation potential of the Rel/p65 subunit of NF-kappa B. Mol. Cell Biol. 20, 1626–1638.
Pap, M. and Cooper, G. M. (1998) Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt survival pathway. J. Biol. Chem. 273, 19,929–19,932.
Zhang, H. M., Rao, J. N., Guo, X., et al. (2004) Akt kinase activation blocks apoptosis in intestinal epithelial cells by inhibiting caspase-3 after polyamine depletion. J. Biol. Chem. 279, 22,539–22,547.
Bhattacharya, S., Ray, R. M., and Johnson, L. R. (2005) Decreased apoptosis in IEC-6 cells following polyamine depletion depends on NF-?B activation but not GSK3β activity. Apoptosis 10, 759–776.
Pfeffer, L. M., Yang, C. H., Pfeffer, S. R., Murti, A., McCormack, S., A., and Johnson, L. R. (2000) Inhibition of ornithine decarboxylase induces STAT3 tyrosine phosphorylation and DNA binding in IEC-6 cells. Am. J. Physiol. Cell Physiol. 278, C331–C335.
Kanda, N., Seno, H., Konda, Y., and Chiba, T. (2004) STAT3 is constitutively activated and supports cell survival in association with surviving expression and in gastric cancer cells. Oncogene 23, 4921–4929.
Bhattacharya, S., Ray, R. M., and Johnson, L. R. (2005) STAT3-mediated transcription of Bcl-2, Mcl-1 and BIRC3 prevents apoptosis in polyamine-depleted cells. Biochem. J. 392, 335–344.
Garcia, A., Cayla, X., Guergnon, J., et al. (2003) Serine/threonine protein phosphatases PP1 and PP2A are key players in apoptosis. Biochimie 85, 721–726.
Tung, H. Y., Pelech, S., Fisher, M. J., Pogson, C. I., and Cohen, P. (1985) The protein phosphatases involved in cellular regulation. Influence of polyamines on the activities of PP-1 and PP2A. Eur. J. Biochem. 149, 305–313.
Cornwell, T., Mehta, P., and Shenolikar, S. (1986) Polyamine stimulation of PP-2A from rat liver using a non-protein phosphoester substrate. J. Cyclic Nacleotide Protein Phosphor. Res. 11, 373–382.
Ray, R. M., Bhattacharya, S., and Johnson, L. R. (2005) Inhibition of PP2A in polyamine depleted cells is responsible for their resistance to apoptosis. J. Biol. Chem. 280, 31,091–31,100.
Chen, J., Martin, B. L., Brautigan, D. L. (1992) Regulation of protein serine-threonine phosphatase type 2A by tyrosine phosphorylation. Science 257, 1261–1264.
Pengetnze, Y., Steed, M., Roby, K. F., Terranova, P. F., and Taylor, C. C. (2003) Src tyrosine kinase promotes survival and resistance to chemotherapeutics in a mouse ovarian cancer cell line. Biochem. Biophys. Res. Commun. 309, 377–383.
Anderson, S. M., Carroll, P. M., and Lee, F. D. (1990) Aborgation of IL-3 dependent growth requires a functional v-Src gene product. Oncogene 5, 317–325.
Gardner, A. M., and Johnson, G. L. (1996) Fibroblast growth factor-2 suppression of TNFα-mediated apoptosis requires Ras and the activation MAP kinase. J. Biol. Chem. 271, 14,560–14,566.
Yao, R. and Cooper, R. M. (1995) Requirement for PI-3 kinase in the prevention of apoptosis by NGF. Science 267, 2003–2006.
Bhattacharya, S., Ray, R. M., and Johnson, L. R. Activation of Src regulates apoptosis in intestinal epithelial cells. In press.
Brown, M. T., and Cooper, J. A. (1996) Regulation, substrates, and functions of Src. Biochim. Biophys. Acta 1287, 121–149.
Gracia, R., Bowman, T. L., Guillian, N., et al. (2001) Constitutive activation of STAT3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20, 2499–2513.
Cao, X., Tay, A., Guy, G. R., and Tan, Y. H. (1996) Activation and association of STAT3 with Src in v-Src transformed cell lines. Mol. Cell Biol. 16, 1595–1603.
Zhang, Y., Turkson, J., Carter-Su, C., et al. (2000) Activation of STAT3 in v-Src-transformed fibroblasts requires cooperation of JAK1 kinase activity. J. Biol. Chem. 275, 24,935–24,944.
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© 2006 Humana Press Inc., Totowa, NJ
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Johnson, L.R., Ray, R.M. (2006). Cellular Signaling and Polyamines in the Control of Apoptosis in Intestinal Epithelial Cells. In: Wang, JY., Casero, R.A. (eds) Polyamine Cell Signaling. Humana Press. https://doi.org/10.1007/978-1-59745-145-1_13
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DOI: https://doi.org/10.1007/978-1-59745-145-1_13
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