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Characterization of Acetoxyscirpendiol of Paecilomyces tenuipes as Inhibitor of Sodium Glucose Co-transporters Expressed in Xenopus laevis Oocytes 원문보기

The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology, v.12 no.4, 2004년, pp.250 - 256  

Park, Il-Woon (Department of Life Sciences, University of Seoul) ,  Hwang, Gwi-Seo (College of Oriental Medicine Kyungwon University) ,  Kim, Ha-Won (Department of Life Sciences, University of Seoul) ,  Lee, Dong-Hee (Department of Life Sciences, University of Seoul)

Abstract AI-Helper 아이콘AI-Helper

Cordyceps possesses numerous health-promoting ingredients including hypoglycemic agents. The mechanism for the reduction of circulatory sugar content, however, is still not fully understand. In this study, 4-beta acetoxyscirpendiol (ASD) was purified from the methanolic extracts from fruiting bodies...

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제안 방법

  • Michaelis-Menten kinetics was obtainined after oocytes were incubated with five different 2-DOG concentrations (5, 15, 30, 60, and 120 mM) for 5 h. Zero trans influx was analyzed using 2-DOG (2 mCi/0.
  • Potential components responsible for reducing blood sugar content, fruiting bodies of P. tenuipes were isogated by methanolic extraction in this study. The 4-beta-acetoxyscirpene-3 alpha, 15-diol (ASD) was subsequently purified from methanolic extracts.
  • Analysis on its chemical structure reveals that ASD belongs to a class of trichothecenes. Since inhibition of the small intestinal Na+/glucose co-transporter (SGLT-1) may help reduce blood-glucose concentration, this study investigates the effect of ASD on the activity of SGLT-1. Since the initial cloning of SGLT-1 from the rabbit small intestine, Xenopus oocyte expression system has been employed to study the functional and structural characteristics of the glucose transporters.
  • This study utilized Xenopus-laevis-oocyte expression system to assay the transport of the glucose analog 2-deoxy-D-glucose and 3-OMG to characterize electrophysiologically the glucosetransport properties of SGLT-1 in the presence of ASD. The results demonstrate that ASD inhibit significantly SGET-Ts activity; thus, glucose transport is severely impaired by ASD.

이론/모형

  • Inhibition of SGLT-1 by ASD analogs. Inhibitory effects by ASD analogs and phloridzin (PZN) on SGLT-1 was measured and compared using voltage clamp methods. The effects of ASD analogs on SGLT-1 were measured in the presence of 50 mM glucose.
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참고문헌 (18)

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  2. Due, A.D., Qu, Z.C., and Thomas, J.M. (1995). Role of the C-terminal tail of the SGLT-l glucose transporter in its expression and function in Xenopus laevis oocytes. Biochemistry 34, 5462-5471 

  3. Jones, K (1997). Cordyceps, Tonic Food of Ancient China, Sylvan Press, Seattle, Washington, pp.52-61 

  4. Juan, M.P., Dong, W., Beatriz, L., Hong, Y., Xia M., Ru, Y., and Darryl, C., (2004) GLUTI deficiency and other glucose transporter diseases. Eur. J. of Endocrin., 150, 627-633 

  5. Kiho, T., Ookubo, K, Usui, S., Ukai, S., Hirano, K (1999) Structural features and hypoglycemic activity of a polysaccharide (CS-FlO) from the cultured mycelium of Cordyceps sinenesis. BioI. Pharm. Bull. 22, 966-970 

  6. Kikuchi, H., Miyagawa, Y., Sahashi, Y., Inatomi, S., Haganuma, A., Nakahata, N., and Oshima, Y. (2004). Novel Spirocyclic Trichothecanes, Spirotenuipesine A and B, Isolated from Entomopathogenic Fungus, Paecilomyces tenuipes. J. Org. Chem.69(2), 352-356 

  7. Kirwan, J. P., and del Aguila, L. F. (2003). Insulin signaling, exercise and cellular integrity. Biochem. Soc. Trans. 31, 1281-1285 

  8. Konno, S., Tortorelis, D.G., Fullerton, S.A., Samadi, A.A., Hettiarachchi, J. and Tazaki, H. (2001) Possible hypoglycemic effect of Maitake mushroom on Type 2 diabetic patients. Diabetic Medicine, 18, 1010-1015 

  9. Lee, D.H. and Kim H.W. (2004) Inhibition of GLUT-l expressed in Xenopus laevis Oocytes by acetoxyscirpendiol of p. tenuipes. J. of Applied Phamocology 12(2), 74-78 

  10. Lee, D.H. (1998). Characterization of 27K zein as a transmembrane protein. J. Biochem. Mol. Biol. 31(2), 196-200 

  11. Lee, D.H., Selester, B., and Pedersen, K. (1995). Free movement of 27K zein in the endoplasmic reticulum. Protein Eng. 9,91-96 

  12. MandaI, A., Verri, T., MandaI, PK, Storelli, C., and Ahearn, GA (2003) Expression of Na(+) /D-glucose cotransport in Xenopus laevis oocytes by injection of poly(A)(+) RNA isolated from lobster (Homarus americanus) hepatopancreas. Comp Biochem Physiol A Mol Integr PhysioL 135(3),467-75 

  13. Nam, K.S., Jo, Y.S., Kim, Y.H., Hyun, J.W., and Kim, H.W. (2001). Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes. Life Sci. 69(2), 229-237 

  14. Oulianova, N., Falk, S., and Berteloot, A .(200l) Two-step mechanism of phroridzin binding to the SGLTl protein in the kidney. J. Membrane BioI. 179,223-242 

  15. Rudlowski C, Becker AJ, Schroder W, Rath W, Buttner R, and Moser M. (2003). GLUTl messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin PatholI 20(5), 691-698 

  16. Rumsey, S. C., Daruwala, R., AI-Hasani, H., Zarnowski, M. J., Simpson, I. A., and Levine, M. (2003). Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J. Biol. Chem. 275, 28246-28253 

  17. Talpur NA, Echard BW, Fan AY, Jaffari O, Bagchi D., and Preuss HG (2002) Antihypertensive and metabolic effects of whole Mitake mushroom powder and its fractions in two rat strains. Mol Cell Biochem. 237, 129-136 

  18. Wood, I.S., and Trayhurn P. (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br. 1. Nutr. 89(1), 3-9 

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