Molecular Changes in Remote Tissues Induced by Electro-Acupuncture Stimulation at Acupoint ST36

  • Rho, Sam-Woong (College of Oriental Medicine, Kyunghee University) ;
  • Choi, Gi-Soon (Department of East-West Medicine Graduate School, Kyunghee University) ;
  • Ko, Eun-Jung (College of Oriental Medicine, Kyunghee University) ;
  • Kim, Sun-Kwang (College of Oriental Medicine, Kyunghee University) ;
  • Lee, Young-Seop (College of Oriental Medicine, Kyunghee University) ;
  • Lee, Hye-Jung (College of Oriental Medicine, Kyunghee University) ;
  • Hong, Moo-Chang (College of Oriental Medicine, Kyunghee University) ;
  • Shin, Min-Kyu (College of Oriental Medicine, Kyunghee University) ;
  • Min, Byung-Il (Department of East-West Medicine Graduate School, Kyunghee University) ;
  • Kee, Hyun-Jung (Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Lee, Cheol-Koo (Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Bae, Hyun-Su (College of Oriental Medicine, Kyunghee University)
  • Received : 2007.06.04
  • Accepted : 2007.11.29
  • Published : 2008.04.30

Abstract

To investigate the effects of electro-acupuncture (EA) treatment on regions remote from the application, we measured cellular, enzymatic, and transcriptional activities in various internal tissues of healthy rats. The EA was applied to the well-identified acupoint ST36 of the leg. After application, we measured the activity of natural killer cells in the spleen, gene expression in the hypothalamus, and the activities of antioxidative enzymes in the hypothalamus, liver and red blood cells. The EA treatment increased natural killer cell activity in the spleen by approximately 44%. It also induced genes related to pain, including 5-Hydroxytryptamine (serotonin) receptor 3a (Htr3a) and Endothelin receptor type B (Ednrb) in the hypothalamus, and increased the activity of superoxide dismutase in the hypothalamus, liver, and red blood cells. These findings indicate that EA mediates its effects through changes in cellular activity, gene expression, and enzymatic activity in multiple remote tissues. The sum of these alterations may explain the beneficial effects of EA.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF), Korea Science and Engineering Foundation

References

  1. Ali, S.F., LeBel, C.P., and Bondy, S.C. (1992). Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13, 637-648
  2. Brunner, K.T., Mauel, J., Cerottini, J.C., and Chapuis, B. (1968). Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology 14, 181-196
  3. Chiu, J.H., Cheng, H.C., Tai, C.H., Hsieh, J.C., Yeh, T.C., Cheng, H., Lin, J.G., and Ho, L.T. (2001). Electroacupuncture- induced neural activation detected by use of manganeseenhanced functional magnetic resonance imaging in rabbits. Am J. Vet. Res. 62, 178-182 https://doi.org/10.2460/ajvr.2001.62.178
  4. Chiu, J.H., Chung, M.S., Cheng, H.C., Yeh, T.C., Hsieh, J.C., Chang, C.Y., Kuo, W.Y., Cheng, H., and Ho, L.T. (2003). Different central manifestations in response to electroacupuncture at analgesic and nonanalgesic acupoints in rats: a manganese-enhanced functional magnetic resonance imaging study. Can. J. Vet. Res. 67, 94-101
  5. Flohe, L., Becker, R., Brigelius, R., Lengfelder, E., and Otting, F. (1988). Convenient assays for superoxide dismutase. CRC handbook of free radicals and antioxidants in biomedicine. 3, 287-293
  6. Flohe, L., Gunzler, W.A., and Schock, H.H. (1973). Glutathione peroxidase: a selenoenzyme. FEBS Lett. 32, 132-134 https://doi.org/10.1016/0014-5793(73)80755-0
  7. Hui, K.K., Liu, J., Marina, O., Napadow, V., Haselgrove, C., Kwong, K.K., Kennedy, D.N., and Makris, N. (2005). The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI. Neuroimage 27, 479-496 https://doi.org/10.1016/j.neuroimage.2005.04.037
  8. Khodorova, A., Navarro, B., Jouaville, L.S., Murphy, J.E., Rice, F.L., Mazurkiewicz, J.E., Long-Woodward, D., Stoffel, M., Strichartz, G.R., Yukhananov, R., et al. (2003). Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat. Med. 9, 1055-1061 https://doi.org/10.1038/nm885
  9. Kim, C.K., Choi, G.S., Oh, S.D., Han, J.B., Kim, S.K., Ahn, H.J., Bae, H., and Min, B.I. (2005a). Electroacupuncture upregulates natural killer cell activity Identification of genes altering their expressions in electroacupuncture induced upregulation of natural killer cell activity. J. Neuroimmunol. 168, 144-153 https://doi.org/10.1016/j.jneuroim.2005.07.005
  10. Kim, S.K., Lee, G., Shin, M., Han, J.B., Moon, H.J., Park, J.H., Kim, K.J., Ha, J., Park, D.S., and Min, B.I. (2006). The association of serum leptin with the reduction of food intake and body weight during electroacupuncture in rats. Pharmacol. Biochem. Behav. 83, 145-149 https://doi.org/10.1016/j.pbb.2006.01.002
  11. Kim, S.K., Park, J.H., Bae, S.J., Kim, J.H., Hwang, B.G., Min, B.I., Park, D.S., and Na, H.S. (2005b). Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors. Exp. Neurol. 195, 430-436 https://doi.org/10.1016/j.expneurol.2005.06.018
  12. Lee, B.H., Jeong, S.M., Lee, J.H., Kim, J.H., Yoon, I.S., Lee, J.H., Choi, S.H., Lee, S.M., Chang, C.G., Kim, H.C., et al. (2005). Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pretransmembrane domain I. Mol. Cells 20, 69-73
  13. Liu, C.Z., Yu, J.C., Zhang, X.Z., Fu, W.W., Wang, T., and Han, J.X. (2006). Acupuncture prevents cognitive deficits and oxidative stress in cerebral multi-infarction rats. Neurosci. Lett. 393, 45-50 https://doi.org/10.1016/j.neulet.2005.09.049
  14. Milligan, E.D., Zapata, V., Chacur, M., Schoeniger, D., Biedenkapp, J., O'Connor, K.A., Verge, G.M., Chapman, G., Green, P., Foster, A.C., et al. (2004). Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Eur. J. Neurosci. 20, 2294-2302 https://doi.org/10.1111/j.1460-9568.2004.03709.x
  15. Pomonis, J.D., Rogers, S.D., Peters, C.M., Ghilardi, J.R., and Mantyh, P.W. (2001). Expression and localization of endothelin receptors: implications for the involvement of peripheral glia in nociception. J. Neurosci. 21, 999-1006 https://doi.org/10.1523/JNEUROSCI.21-03-00999.2001
  16. Radhakrishnan, R., King, E.W., Dickman, J.K., Herold, C.A., Johnston, N.F., Spurgin, M.L., and Sluka, K.A. (2003). Spinal 5-HT(2) and 5-HT(3) receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats. Pain 105, 205-213 https://doi.org/10.1016/S0304-3959(03)00207-0
  17. Sato, T., Yu, Y., Guo, S.Y., Kasahara, T., and Hisamitsu, T. (1996). Acupuncture stimulation enhances splenic natural killer cell cytotoxicity in rats. Jpn. J. Physiol. 46, 131-136 https://doi.org/10.2170/jjphysiol.46.131
  18. Vandesompele, J., De Paepe, A., and Speleman, F. (2002). Elimination of primer-dimer artifacts and genomic coamplification using a two-step SYBR green I real-time RT-PCR. Anal. Biochem. 303, 95-98 https://doi.org/10.1006/abio.2001.5564
  19. Witt, C., Brinkhaus, B., Jena, S., Linde, K., Streng, A., Wagenpfeil, S., Hummelsberger, J., Walther, H.U., Melchart, D., and Willich, S.N. (2005). Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet 366, 136-143 https://doi.org/10.1016/S0140-6736(05)66871-7
  20. Yu, Y., Kasahara, T., Sato, T., Guo, S.Y., Liu, Y., Asano, K., and Hisamitsu, T. (1997). Enhancement of splenic interferongamma, interleukin-2, and NK cytotoxicity by S36 acupoint acupuncture in F344 rats. Jpn. J. Physiol. 47, 173-178 https://doi.org/10.2170/jjphysiol.47.173