Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지

Regulation of LPS-induced Nitric Oxide Synthase Activity by Cigarette Smoke in Mouse Brain

  • Published : 2006.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Nitric oxide(nitrogen monoxide, NO) plays important physiological roles, but excessive generation can be toxic. NO is present in cigarette smoke at up to 1,000 ppm, and probably represents one of the greatest exogenous sources of NO to which humans are exposed. We investigated whether cigarette smoking reduces the production of endogenous NO and whether it influences the action of lipopolysaccharide(LPS) to induce nitric oxide synthase activity in mouse brain. Mice(C57BL6/J) were exposed to cigarette smoke for 8 weeks. LPS was injected intraperitoneally in single or combination with the exposure to cigarette smoke. Six hours after the injection of LPS, mice were sacrificed and sera and brains were collected. Serum concentrations of nitrate and nitrite were not charged by 4-week smoke exposure, but were significantly increased by 6 and 8 weeks of smoke exposure. Interestingly, cigarette smoke reduced the elevation in serum nitrate and nitrite concentrations produced by LPS after 4-week smoking exposure. NO synthase(NOS) activity in brain was upregulated by LPS-administration. However, cigarette smoke exposure remarkably and consistently decreased the LPS-induced activity in mouse brain. This result suggests that cigarette smoking may affect against overproduction of the endogenous NO by LPS through the inhibition of NOS activity induced by LPS in brain or by modulation of the LPS action for the induction of NOS activity. We also suggest the possibility that the exogenous NO evolved in cigarette smoke enables feedback inhibition of NOS activity or other possibility that it attenuates the toxicity of endotoxin LPS in vivo by unknown mechanisms, which should be further studied.

Keywords

References

  1. Arnold, W.P., Aldred, R. and Murad, F. (1977): Cigarette smoke activates guanylate cyclase and increases guanosine 3',5'-monophosphate in tissues. Science, 198, 934-936 https://doi.org/10.1126/science.22126
  2. Assreuy, M., Cunha, F.Q., Liew, F.Y. and Moncada, S. (1993): Feedback inhibition of nitric oxide synthase activity by nitric oxide. Br. J. Pharmacol., 108, 833-837 https://doi.org/10.1111/j.1476-5381.1993.tb12886.x
  3. Borkhoven, C. and Niessen, H.J. (1961): Amounts of oxide of nitrogen and carbon monoxide in cigarette smoke, with or without inhalation. Nature, 192, 458-459 https://doi.org/10.1038/192458a0
  4. Bredt, D.S. and Snyder, S.H. (1992): Nitric oxide, a novel neuronal messenger. Neuron, 8, 3-11 https://doi.org/10.1016/0896-6273(92)90104-L
  5. Buga, G.M., Griscavage, J.M., Rogers, N.E. and Ignarro, L.J. (1993): Negative feedback inhibition of endothelial cell function by nitric oxide. Circ. Res., 73, 808-812 https://doi.org/10.1161/01.RES.73.5.808
  6. Bult, H., Boeckxstaens, G.E., Pelckmans, P.A., Jordaens, F.H., Van Maercke, Y.M. and Herman, A.G. (1990): Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature (London), 345, 346-347 https://doi.org/10.1038/345346a0
  7. Burnett, A. L., Lowenstein, C. J., Bredt, D. S., Chang, T. S. K., and Snyder, S. H. (1992) Nitric oxide: a physiologic mediator of penile erection. Science 257, 401-403 https://doi.org/10.1126/science.1378650
  8. Desai, K.M., Sessa, W.C. and Vane, J.R. (1991): Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature (London), 351, 477-479 https://doi.org/10.1038/351477a0
  9. Diana, J.N. and Vaught, A. (1990): Research Cigarettes. Lexington, KY, USA: University of Kentucky Printing Services
  10. Galea, E., Feinstein, D.L. and Reis, D.J. (1992): Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Proc. Natl. Acad. Sci. USA, 89, 10945-10949
  11. Galea, E., Reis, D.J. and Feinstein, D.L. (1994): Cloning and expression of inducible nitric oxide synthase from rat astrocytes. J. Neurosci. Res., 37, 406-414 https://doi.org/10.1002/jnr.490370313
  12. Green, L.C., Wagner, D.A., Glogowski, J., Skipper, P.L., Wishnok, J.S. and Tannenbaum S.R. (1982): Analysis of nitrate, nitrite, and [$^{15}N$]nitrate in biological fluids. Anal. Biochem., 126, 131-138 https://doi.org/10.1016/0003-2697(82)90118-X
  13. Gruetter, C.A., Barry, B.K., McNamara, D.B., Kadowitz, P.J. and Ignarro, L.J. (1980): Coronary arterial relaxation and guanylate cyclase activation by cigarette smoke. J. Pharmacol. Exp. Ther., 214, 9-15
  14. Hattori, Y., Hattori, S., Motohashi, S., Kasai, K., Shimoda, S.I. and Nakanishi, N. (1997): Co-induction of nitric oxide and tetrahydrobiopterin synthesis in the myocardium in vivo. Mol. Cell Biochem., 166, 177-181 https://doi.org/10.1023/A:1006875707028
  15. Hill, G., Ruggeroli, A., Pohorecki, R., Alonso, A. and Robbins, R.A. (1995): Cigarette smoking reduces endogenous airway nitric oxide production during cardiopulmonary bypass in humans. Anesth. Analg., 81, 170-172 https://doi.org/10.1097/00000539-199507000-00034
  16. Hope, B.T., Michael, G.J., Knigge, K.M. and Vincent, S.R. (1991): Neuronal NADPH diaphorase is a nitric oxide synthase. Proc. Natl. Acad. Sci. USA, 88, 2811-2814
  17. Ignarro, L.J. (1989): Endothelium-derived nitric oxide: actions and properties. FASEB J., 3, 31-36 https://doi.org/10.1096/fasebj.3.1.2642868
  18. Jungersten, L., Edlund, A., Petersson, A.S. and Wennmalm, A. (1993): Plasma nitrate as an index of endogenous nitric oxide formation in man. Analysis of kinetics, confounding factors, and response to immunological challenge. Circulation, 88, I-369
  19. Kharitonov, S.A., Robbins, R.A., Yates, D., Keatings, V. and Barnes, P.J. (1995): Acute and chronic effects of cigarette smoking on exhaled nitric oxide. Am. J. Respir. Crit. Care Med., 152, 609-612 https://doi.org/10.1164/ajrccm.152.2.7543345
  20. Koprowski, H., Zheng, Y.M., Heber-Katz, E., Fraser, N., Rorke, L., Fu, Z.F., Hanlon, C. and Dietzschold, B. (1993): In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases. Proc. Natl. Acad. Sci. USA, 90, 3024-3027
  21. Leblanc, R., Xie, J., Warner, A., Kolls, J., Shellito J., Malinski, T., Summer, W.R. and Greenberg, S. (1992): Nitric oxide derived from macrophages rather than neutrophils mediates endotoxin-induced hypotension. Clin. Res., 40, 777A
  22. Lee, S., Barbanel, G. and River, C. (1995): Systemic endotoxin increases steady-state gene expression of hypothalamic nitric oxide synthase: comparison with corticotropinreleasing factor and vasopressin gene transcripts. Brain Res., 705, 136-148 https://doi.org/10.1016/0006-8993(95)01142-0
  23. Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951): Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265-275
  24. Maines, M.D. (1988): Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J., 2, 2557-2568 https://doi.org/10.1096/fasebj.2.10.3290025
  25. Moncada, S., Palmer, R.M. and Higgs, E.A. (1991): Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev., 43, 109-142
  26. Nathan, C.F. (1992): Nitric oxide as a secretory product of mammalian cells. FASEB J., 6, 3051-3064 https://doi.org/10.1096/fasebj.6.12.1381691
  27. Nathan, C.F. and Hibbs, J.B. Jr. (1991): Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opin. Immunol., 3, 65-70 https://doi.org/10.1016/0952-7915(91)90079-G
  28. Nathan, C.F. and Xie, Q.-W. (1994): Nitric oxide synthases Roles, tolls, and controls. Cell, 78, 915-918 https://doi.org/10.1016/0092-8674(94)90266-6
  29. Norman, V. and Keith, C.H. (1965): Nitrogen oxides in tobacco smoke. Nature, 205, 915-916
  30. Nowicki, J.P., Duval, D., Poignet, H. and Scatton, B. (1991): Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur.J. Pharmacol., 204, 339-340 https://doi.org/10.1016/0014-2999(91)90862-K
  31. Persson, M.G. and Gustafsson, L.E. (1993): Allergen-induced airway obstruction in guinea-pigs is associated with changes in nitric oxide levels in exhaled air. Acta Physiol. Scand., 149, 461-466 https://doi.org/10.1111/j.1748-1716.1993.tb09643.x
  32. Persson, M.G., Zetterstrom, O., Agrenius, V., et al. (1994): Single-breath nitric oxide measurements in asthmatic patients and smokers. Lancet, 343, 146-147 https://doi.org/10.1016/S0140-6736(94)90935-0
  33. Rengasamy, A. and Johns, R.A. (1994): Regulation of nitric oxide synthase by nitric oxide. Mol. Pharmacol., 44, 124-128
  34. Robbins, R.A., Hamel, F.G., Floreani, A.A. et al. (1993): Bovine bronchial epithelial cells metabolize L-arginine to L-citrulline: possible role of nitric oxide synthase. Life Sci., 52, 709-716 https://doi.org/10.1016/0024-3205(93)90232-R
  35. Salter, M., Knowles, R.G. and Moncada, S. (1991): Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett., 291, 145-149 https://doi.org/10.1016/0014-5793(91)81123-P
  36. Schilling, J., Holzer, P., Guggenbach, M., Gyurech, D., Marathia, K. and Geroulanos, S. (1994): Reduced endogenous nitric oxide in the exhaled air of smokers and hypertensives. Eur. Respir. J., 7, 467-471 https://doi.org/10.1183/09031936.94.07030467
  37. Sherman, P.A., Laubach, V.E., Reep, B.R. and Wood, E.R. (1993): Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry, 32,11600-11605 https://doi.org/10.1021/bi00094a017
  38. Verma, A., Hirsch, D.J., Glatt, C.E., Ronnett, G.V. and Snyder, S.H. (1993): Carbon monoxide:a putative neural messenger. Science, 259, 381-384 https://doi.org/10.1126/science.7678352
  39. Wennmalm, A., Benthin, G. Edlund, A. Jungersten, L. Kieler- Jensen, N. Lundin, S. Westfelt, U.N., Petersson, A.S. and Waagstein, F. (1993): Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. Circ. Res., 73, 1121-1127 https://doi.org/10.1161/01.RES.73.6.1121
  40. White, K.A. and Marletta, M.A. (1992): Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemisty, 31, 6627-6631 https://doi.org/10.1021/bi00144a001
  41. Wright, C.E., Rees, D.D. and Moncada, S. (1992): Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc. Res., 26, 48-57 https://doi.org/10.1093/cvr/26.1.48
  42. Zielasek, J., Tausch, M., Toyka, K. and Hartung, H.P. (1992): Production of nitrite by neonatal rat microglial cells/brain macrophages. Cell Immunol., 141, 111-120 https://doi.org/10.1016/0008-8749(92)90131-8