Skip to main content
SpringerLink
Log in

Sesamol induces nitric oxide release from human umbilical vein endothelial cells

  • Articles
  • Published:
Lipids

Abstract

Sesamol, which is derived from sesame seed lignans, is reportedly an antioxidant. Nitric oxide (NO), the most important vascular relaxing factor, is regulated in the endothelium. In addition, NO is involved in protecting endothelium and has antiatherosclerotic and antithrombotic activities. The endothelium produces NO through the regulation of both endothelial NO synthase (eNOS) expression and activity in endothelial cells. This study sought to investigate the effect of sesamol on NO released from human umbilical vein endothelial cells (HUVEC) and to examine the expression and activity of eNOS. Sesamol induced NO release from endothelial cells in a dose-dependent manner (from 1 to 10 μM), as measured 24 h after treatment; the expression of the eNOS gene at both transcription and translation levels; and NOS activity in endothelial cells. The content of cGMP was also increased by sesamol through NO signaling. The transcription of eNOS induced by sesamol was confirmed through the activation of PI-3 kinase-Akt (protein kinase B) signaling. The results demonstrate that sesamol induces NOS signaling pathways in HUVEC and suggest a role for sesamol in cardiovascular reactivity in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Akt:

protein kinase B

EC:

endothelial cell

ECE-1:

endothelin-converting enzyme-1

ECL:

enhanced chemiluminescence

EDRF:

endothelium-derived relaxing factor

EIA:

enzyme-linked immunosorbent assay

eNOS (=NOS3):

endothelial NO synthase

ET-1:

endothelin-1

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

HUVEC:

human umbilical vein endothelial cells

L-NAME:

Nω-nitro-l-arginine methyl ester

NO:

nitric oxide

NOS:

nitric oxide synthase

PA:

plasminogen activator

PI-3K:

PI-3 kinase

PVDF:

polyvinylidene difluoride

ROS:

reactive oxygen species

RT:

reverse transcription

SSC:

saline-sodium citrate

TBST:

Trisbuffered saline Tween-20

tPA:

tissue plasminogen activator; uPA urokinase plasminogen activator

VSMC:

vascular smooth muscle cells

References

  1. Fukuda, Y., Nagata, M., Osawa, T., and Namiki, M. (1986) Chemical Aspects of the Antioxidative Activity of Roasted Sesame Seed Oil and the Effect of Using the Oil for Frying, Agric. Biol. Chem. 50, 857–862.

    CAS  Google Scholar 

  2. Fukuda, Y., Nagata, M., Osawa, T., and Namiki, M. (1986) Contribution of Lignan Analogues to Antioxidative Activity of Refined Unroasted Sesame Seed Oil, J. Am. Oil Chem. Soc. 63, 1027–1031.

    Article  CAS  Google Scholar 

  3. Kita, S., Matsumura, Y., Morimoto, S., Akimoto, K., Furuya, M., Oka, N., and Tanaka, T. (1995) Antihypertensive Effect of Sesamin. II. Protection Against Two-Kidney, One-Clip Renal Hypertension and Cardiovascular Hypertrophy, Biol. Pharm. Bull. 18, 1283–1285.

    PubMed  CAS  Google Scholar 

  4. Matsumura, Y., Kita, S., Morimoto, S., Akimoto, K., Furuya, M., Oka, N., and Tanaka, T. (1995) Antihypertensive Effect of Sesamin. Protection Against Deoxycorticosterone Acetate-Salt-Induced Hypertension and Cardiovascular Hypertrophy, Biol. Pharm. Bull. 18, 1016–1019.

    PubMed  CAS  Google Scholar 

  5. Matsumura, Y., Kita, S., Ohgushi, R., and Okui, T. (2000) Effects of Sesamin on Altered Vascular Reactivity in Aortic Rings of Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rat, Biol. Pharm. Bull. 23, 1041–1045.

    PubMed  CAS  Google Scholar 

  6. Matsumura, Y., Kita, S., Tanida, Y., Taguchi, Y., Morimoto, S., Akimoto, K., and Tanaka, T. (1998) Antihypertensive Effect of Sesamin. III. Protection Against Development and Maintenance of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats, Biol. Pharm. Bull. 21, 469–473.

    PubMed  CAS  Google Scholar 

  7. Nakano, D., Itoh, C., Takaoka, M., Kiso, Y., Tanaka, T., and Matsumura, Y. (2002) Antihypertensive Effect of Sesamin. IV. Inhibition of Vascular Superoxide Production by Sesamin, Biol. Pharm. Bull. 25, 1247–1249.

    Article  PubMed  CAS  Google Scholar 

  8. Noguchi, T., Ikeda, K., Sasaki, Y., Yamamoto, J., Seki, J., Yamagata, K., Nara, Y., Hara, H., Kakuta, H., and Yamori, Y. (2001) Effects of Vitamin E and Sesamin on Hypertension and Cerebral Thrombogenesis in Stroke-Prone Spontaneously Hypertensive Rats, Hypertens. Res. 24, 735–742.

    Article  PubMed  CAS  Google Scholar 

  9. Nakai, M., Harada, M., Nakahara, K., Akimoto, K., Shibata, H., Miki, W., and Kiso, Y. (2003) Novel Antioxidative Metabolites in Rat Liver with Ingested Sesamin, J. Agric. Food Chem. 51, 1666–1670.

    Article  PubMed  CAS  Google Scholar 

  10. Shimizu, S., Akimoto, K., Shinmen, Y., Kawashima, H., Sugano, M., and Yamada, H. (1991) Sesamin Is a Potent and Specific Inhibitor of Δ5 Desaturase in Polyunsaturated Fatty Acid Biosynthesis, Lipids 26, 512–516.

    PubMed  CAS  Google Scholar 

  11. Hirose, N., Inoue, T., Nishihara, K., Sugano, M., Akimoto, K., Shimizu, S., and Yamada, H. (1991) Inhibition of Cholesterol Absorption and Synthesis in Rats by Sesamin, J. Lipid Res. 32, 629–638.

    PubMed  CAS  Google Scholar 

  12. Uchida, M., Nakajin, S., Toyoshima, S., and Shinoda, M. (1996) Antioxidative Effect of Sesamol and Related Compounds on Lipid Peroxidation, Biol. Pharm. Bull. 19, 623–626.

    PubMed  CAS  Google Scholar 

  13. Jacklin, A., Ratledge, C., Welham, K., Bilko, D., and Newton, C.J. (2003) The Sesame Seed Oil Constituent, Sesamol, Induces Growth Arrest and Apoptosis of Cancer and Cardiovascular Cells, Ann. N.Y. Acad. Sci. 1010, 374–380.

    Article  PubMed  CAS  Google Scholar 

  14. Chen, P.R., Lee, C.C., Chang, H., and Tsai, C.E. (2005) Sesamol Regulates Plasminogen Activator Gene Expression in Cultured Endothelial Cells: A Potential Effect on Fibrinolytic System, J. Nutr. Biochem. 16, 59–64.

    Article  PubMed  CAS  Google Scholar 

  15. Furchgott, R.F., and Zawadzky, J.V. (1980) The Obligatory Role of Endothelial Cells in the Relaxation of Arterial Smooth Muscle by Acetylcholine, Nature 288, 373–376.

    Article  PubMed  CAS  Google Scholar 

  16. Palmer, R.M.J., Ferrige, A.G., and Moncada, S. (1987) Nitric Oxide Release Accounts for the Biological Activity of Endothelium-Derived Relaxing Factor, Nature 327, 524–526.

    Article  PubMed  CAS  Google Scholar 

  17. Palmer, R.M.J., Ashton, D.S., and Moncada, S. (1988) Vascular Endothelial Cells Synthesize Nitric Oxide from l-Arginine, Nature 333, 664–666.

    Article  PubMed  CAS  Google Scholar 

  18. Bredt, D.S., Hwang, P.M., Glatt, C.E., Lowenstein, C., Reed, R.R., and Snyder, S.H. (1991) Cloned and Expressed Nitric Oxide Synthase Structurally Resembles Cytochrome P-450 Reductase, Nature 351, 714–718.

    Article  PubMed  CAS  Google Scholar 

  19. Denninger, J.W., and Marletta, M.A. (1999) Guanylate Cyclase and NO/cGMP Signaling Pathway, Biochim. Biophys. Acta 1441, 334–350.

    Google Scholar 

  20. Cooke, J.P., Singer, A.H., Tsao, P., Zera, P., Rowan, R.A., and Billingham, M.E. (1992) Antiatherogenic Effects of l-Arginine in the Hypercholesterolemic Rabbit, J. Clin. Invest. 90, 1168–1172.

    PubMed  CAS  Google Scholar 

  21. Shultz, P.J., and Raij, L. (1992) Endogenously Synthesized Nitric Oxide Prevents Endotoxin-Induced Glomerular Thrombosis, J. Clin. Invest. 90, 1718–1725.

    PubMed  CAS  Google Scholar 

  22. Wink, D.A., Hanbauer, I., Krishna, M.C., DeGraff, W., Gamson, J., and Mitchell, J.B. (1993) Nitric Oxide Protects Against Cellular Damage and Cytotoxicity from Reactive Oxygen Species, Proc. Natl. Acad. Sci. USA 90, 9813–9817.

    Article  PubMed  CAS  Google Scholar 

  23. Dimmeler, S., and Zeiher, A.M. (1999) Nitric Oxide—An Endothelial Cell Survival Factor, Cell Death Differ. 6, 964–968.

    Article  PubMed  CAS  Google Scholar 

  24. Lee, C.C., Shyu, K.G., Lin, S., Wang, B.W., Liu, Y.C., and Chang, H. (2002) Cell Adhesion Regulates the Plasminogen Activator Inhibitor-1 Gene Expression in Anchorage-Dependent Cells, Biochem. Biophys. Res. Commun. 291, 185–190.

    Article  PubMed  CAS  Google Scholar 

  25. Maniatis, T., Fritsch, E.F., and Sambrook, J. (1989) Extraction, Purification, and Analysis of Messenger RNA from Eukaryotic Cells, in Molecular Cloning, A Laboratory Manual, pp. 7.1–7.87, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.

    Google Scholar 

  26. Dimmeler, S., Fisslthaler, B., Fleming, I., Hermann, C., Busse, R., and Zeiher, A.M. (1999) Activation of Nitric Oxide Synthase in Endothelial Cells via Akt-Dependent Phosphorylation, Nature 399, 601–605.

    Article  PubMed  CAS  Google Scholar 

  27. Fulton, D., Gratton, J.P., McCabe, T.J., Fontana, J., Fujio, Y., Walsh, K., Franke, T.F., Papapetropoulos, A., and Sessa, W.C. (1999) Regulation of Endothelium-Derived Nitric Oxide Production by the Protein Kinase Akt, Nature 399, 597–601.

    Article  PubMed  CAS  Google Scholar 

  28. Hashiguchi, A., Yano, S., Morioka, M., Hamada, J., Ushio, Y., Takeuchi, Y., and Fukunaga, K. (2004) Up-regulation of Endothelial Nitric Oxide Synthase via Phosphatidylinositol 3-Kinase Pathway Contributes to Ischemic Tolerance in the CA1 Subfield of Gerbil Hippocampus, J. Cereb. Blood Flow Metab. 24, 271–279.

    Article  PubMed  CAS  Google Scholar 

  29. Cieslik, K., Abrams, C.S., and Wu, K.K. (2001) Up-regulation of Endothelial Nitric-Oxide Synthase Promoter by the Phosphatidylinositol 3-Kinase γ/Janus Kinase 2/MEK-1-Dependent Pathway, J. Biol. Chem. 276, 1211–1219.

    Article  PubMed  CAS  Google Scholar 

  30. Lee, C.C., Chen, P.R., Lin, S., Tsai, S.C., Wang, B.W., Chen, W.W., Tsai, C.E., and Shyu, K.G. (2004) Sesamin Induces Nitric Oxide and Decreases Endothelin-1 Production in HUVECs: Possible Implications for Its Antihypertensive Effect, J. Hypertens. 22, 2329–2338.

    Article  PubMed  CAS  Google Scholar 

  31. Tiefenbacher, C.P., and Kreuzer, J. (2003) Nitric Oxide-Mediated Endothelial Dysfunction—Is There Need to Treat? Curr. Vasc. Pharmacol. 1, 123–133.

    Article  PubMed  CAS  Google Scholar 

  32. Chang, J., Rao, N.V., Markewitz, B.A., Hoidal, J.R., and Michael, J.R. (1996) Nitric Oxide Donor Prevents Hydrogen Peroxide-Mediated Endothelial Cell Injury, Am. J. Physiol. 270, L931-L940.

    PubMed  CAS  Google Scholar 

  33. Grosser, N., and Schroder, H. (2003) Aspirin Protects Endothelial Cells from Oxidant Damage via the Nitric Oxide-cGMP Pathway, Arterioscler. Thromb. Vasc. Biol. 23, 1345–1351.

    Article  PubMed  CAS  Google Scholar 

  34. Polte, T., Oberle, S., and Schröder, H. (1997) Nitric Oxide Protects Endothelial Cells from Tumor Necrosis Factor-Mediated Cytotoxicity: Possible Involvement of Cyclic GMP, FEBS Lett. 409, 46–48.

    Article  PubMed  CAS  Google Scholar 

  35. Wink, D.A., Cook, J.A., Pacelli, R., DeGraff, W., Gamson, J., Liebmann, J., Krishna, M.C., and Mitchell, J.B. (1996) The Effect of Various Nitric Oxide-Donor Agents on Hydrogen Peroxide-Mediated Toxicity: A Direct Correlation Between Nitric Oxide Formation and Protection, Arch. Biochem. Biophys. 331, 241–248.

    Article  PubMed  CAS  Google Scholar 

  36. McCarty, M.F. (2004) Optimizing Endothelial Nitric Oxide Activity May Slow Endothelial Aging, Med. Hypotheses 63, 719–723.

    Article  PubMed  CAS  Google Scholar 

  37. Dimmeler, S., Haendeler, J., Nehls, M., and Zeiher, A.M. (1997) Suppression of Apoptosis by Nitric Oxide via Inhibition of ICE-like and CPP32-like Proteases, J. Exp. Med. 185, 601–608.

    Article  PubMed  CAS  Google Scholar 

  38. Shiojima, I., and Walsh, K. (2002) Role of Akt Signaling in Vascular Homeostasis and Angiogenesis, Circ. Res. 90, 1243–1250.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition and Food Science, Fu Jen Catholic University, Taipei, Taiwan

    Pey-Rong Chen & Tsuei-Ling Liu

  2. Department of Dietetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    Pey-Rong Chen & Tsuei-Ling Liu

  3. Department of Bioscience Technology, Chung Yuan University, Taoyan, Taiwan

    Chingmin E. Tsai

  4. Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Hang Chang & Chun-Chung Lee

  5. Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

    Chun-Chung Lee

Authors
  1. Pey-Rong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chingmin E. Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tsuei-Ling Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chun-Chung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chun-Chung Lee.

About this article

Cite this article

Chen, PR., Tsai, C.E., Chang, H. et al. Sesamol induces nitric oxide release from human umbilical vein endothelial cells. Lipids 40, 955–961 (2005). https://doi.org/10.1007/s11745-005-1456-3

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-005-1456-3

Keywords

Search

Navigation