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Inhibitory Effect of Nicotine on Apoptosis Induced by Endoplasmic Reticulum Stress

  • Lee, Dong-Hee (Department of Life Sciences, University of Seoul)
  • Published : 2007.12.31

Abstract

Cigarette smoking causes serious health problems in humans, especially if smoking habits are established during their adolescence. Nicotine is known to mutate DNA and interfere with apoptosis. Apoptosis is considered as a potent defense mechanism against cellular damaging agents. This study aims to investigate the effect of nicotine on the progression of apoptosis induced under ER stress conditions using four different established cell lines: HEK293, 3T3-L1, C2C12, and HepG2. When treated with nicotine, the progression of apoptosis was notably inhibited in the four cell lines according to the assays of caspase-3 activation and DNA fragmentation. In ER-stressed cells, nicotine appears to inhibit the progression of apoptosis in a concentration-dependent manner. When cells were treated with nicotine prior to ER stress, GRP94 level significantly increased compared to other ER stress markers of PDI and GRP78. This observation suggests that the inhibitory effect of nicotine may results from up-regulation of GRP94, an anti-apoptotic chaperone, under nicotine treatment. Taken together, the present study strongly implies that nicotine may inhibit apoptosis, caused by prolonged ER stress, based on promotion of GRP94 expression.

References

  1. Blackburn, C. W., Peterson, C. A., Hales, H. A., Carrell, D. T., Jones, K. P., Urry, R. L. and Peterson, C. M. (1994). Nicotine has a direct toxic effect on ovarian function in the immature gonadotropin-stimulated rat. Reprod. Toxicol. 8, 325-331 https://doi.org/10.1016/0890-6238(94)90048-5
  2. Chin, T. Y., Lin H. C., Kuo J. P. and Chueh, S. H. (2007). Dual effect of thapsigargin on cell death in porcine aortic smooth muscle cells. Am J Physiol Cell Physiol, 292, 383 - 395
  3. Chung, F. L. (1999). The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black tea. Proc. Soc. Exp. Biol. Med. 220, 244-248 https://doi.org/10.3181/00379727-220-44374
  4. Chung, F. L., Wang M., Rivenson, A., Iatropoulos, M. J., Reinhardt, J. C., Pittman, B., Ho, C. T. and Amin, S. G. (1998). Inhibition of lung carcinogenesis by black tea in Fischer rats treated with a tobacco-specific carcinogen: caffeine as an important constituent. Cancer Res. 58(18), 4096-4101
  5. Fassina G., Vene R., Morini M., Minghelli S., Benelli R., Noonan D. M. and Albini A. (2004). Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin- 3-gallate. Clin Cancer Res. 14, 4865-4873
  6. Fujiki, H., Suganuma, M., Okabe, S., Sueoka, N., Komori, A., Sueoka, E., Kozu, T., Tada, Y., Suga, K., Imai, K., and Nakachi, K. (1998). Cancer inhibition by green tea. Mutat. Res. 18, 307-310
  7. Gupta, P. C., Murti, P. R., and Bhonsle, R. B. (1996). Epidemiology of cancer by tobacco products and the significance of TSNA. Crit. Rev. Toxicol. 26, 183-198 https://doi.org/10.3109/10408449609017930
  8. Hasseus, B., Wallstrom, M., Osterdahl, B. G., Hirsch J. M. and Jontell M. (1997). Immunotoxic effects of smokeless tobacco on the accessory cell function of rat oral epithelium. Eur. J. Oral Sci. 105, 45-51 https://doi.org/10.1111/j.1600-0722.1997.tb00179.x
  9. Kalra, R., Singh, S. P., Savage, S. M., Sopori, M. L. and Finch, G.L. (2000). Effects of cigarette smoke on immune response: chronic exposure to cigarette smoke impairs antigen-mediated signaling in T cells and depletes IP3-sensitive Ca($2^+) stores. J. Pharmacol. Exp. Ther. 293, 166-171
  10. Karaskov, E., Scott, C., Zhang, L., Ravazzola, T. M. And Volchuk, A. (2007). Chronic Palmitate But Not Oleate Exposure Induces Endoplasmic Reticulum Stress, Which May Contribute to INS-1 Pancreatic {beta}-Cell Apoptosis. Endocrinology, 147, 3398 - 3407 https://doi.org/10.1210/en.2005-1494
  11. Lackmann, G. M., Salzberger, U., Tollner, U., Chen, M., Carmella, S. G. and Hecht, S. S. (1999). Metabolites of a tobacco-specific carcinogen in urine from newborns. J. Natl. Cancer Inst. 91, 459-65 https://doi.org/10.1093/jnci/91.5.459
  12. Malik, A., Azam, S., Hadi, N. and Hadi, S. M. (2003). DNA degradation by water extract of green tea in the presence of copper ions: implications for anticancer properties. Phytother. Res. 17, 358-363 https://doi.org/10.1002/ptr.1149
  13. Mussmann, R., Geese, M., Harder, F., Kegel, S., Andag, U., Lomow, A., Burk, U., Onichtchouk, D., Dohrmann, C. and Austen, M. (2007). Inhibition of GSK3 Promotes Replication and Survival of Pancreatic Beta Cells. J. Biol. Chem. 282, 12030-12037 https://doi.org/10.1074/jbc.M609637200
  14. Palermo, C. M., Hernando J. I., Dertinger S. D., Kende A. S. and Gasiewicz T. A. (2003). Identification of potential aryl hydrocarbon receptor antagonists in green tea. Chem Res Toxicol. 16. 865-872 https://doi.org/10.1021/tx025672c
  15. Poirier, M. C., Santella R. M. and Weston, A. (2000). Carcinogen macromolecular adducts and their measurement Carcinogenesis, 21, 353-359 https://doi.org/10.1093/carcin/21.3.353
  16. Prokopczyk, B., Cox, J. E., Hoffmann, D. and Waggoner S. E. (1997). Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J. Natl. Cancer Inst. 89, 868-873 https://doi.org/10.1093/jnci/89.12.868
  17. Schuller, H. M., McGavin, M. D., Orloff, M., Riechert, A., and Porter, B. (1995). Simultaneous exposure to nicotine and hyperoxia causes tumors in hamsters. Lab. Invest. 73, 448-456
  18. Toda, S. (2004). Inhibitory effects of polyphenols in leaves of Artemisia princeps PAMP on protein fragmentation by Cu(II)- $H_2O_2$ in vitro. J Med. Food. 7, 52-54 https://doi.org/10.1089/109662004322984707
  19. Wynder, E. L., and Muscat, J. E. (1995). The changing epidemiology of smoking and lung cancer histology. Environ. Health Perspect. 103 Suppl. 8, 143-148 https://doi.org/10.1289/ehp.95103s2143
  20. Yung, H. W., Korolchuk, S. Tolkovsky, A. M., Charnock-Jones, D. S. and Burton, G. J. (2007). Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells. FASEB J., 21, 872 - 884 https://doi.org/10.1096/fj.06-6054com