This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nonaka, H. Articles by Yokoyama, M. Search for Related Content PubMed PubMed Citation Articles by Nonaka, H. Articles by Yokoyama, M. Related Collections Risk Factors Cell biology/structural biology Gene regulation

(Circulation. 2001;104:1165.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Taurine Prevents the Decrease in Expression and Secretion of Extracellular Superoxide Dismutase Induced by Homocysteine

Amelioration of Homocysteine-Induced Endoplasmic Reticulum Stress by Taurine

Hidemi Nonaka, MD; Takeshi Tsujino, MD, PhD; Yasuhiro Watari, MD, PhD; Noriaki Emoto, MD, PhD; Mitsuhiro Yokoyama, MD, PhD

From the Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Correspondence to Takeshi Tsujino, MD, PhD, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki, Chuo, Kobe, 650-0017, Japan. E-mail hidemin{at}med.kobe-u.ac.jp

Background—— Hyperhomocysteinemia is an independent risk factor for atherosclerosis. Homocysteine has been shown to induce endoplasmic reticulum (ER) stress in vascular endothelial cells. ER stress is a condition in which glycoprotein trafficking is disrupted and unfolded proteins accumulate in the ER. ER molecular chaperons, such as GRP78, are induced and an ER resident kinase, PERK, is activated when cells are subjected to ER stress. Conversely, taurine is reported to have antiatherogenic effects by unknown mechanisms. To elucidate the mechanisms by which homocysteine induces atherosclerosis and taurine prevents it, we examined whether homocysteine and taurine affect the expression and secretion of extracellular superoxide dismutase (EC-SOD), a glycoprotein secreted from vascular smooth muscle cells (VSMCs) that protects the vascular wall from oxidative stress.

Methods and Results—— We assessed the expression of EC-SOD and GRP78 mRNA in cultured rat VSMCs by Northern blot analysis. The EC-SOD protein secreted into the culture medium was examined by Western blot analysis. Homocysteine (5 mmol/L) and other ER stress inducers, including A23187, were found to decrease EC-SOD mRNA expression and protein secretion. Furthermore, they upregulated GRP78 mRNA expression and activated PERK. Taurine (0.5 to 10 mmol/L), conversely, prevented these actions induced by homocysteine.

Conclusions—— Homocysteine induces ER stress and reduces the secretion and expression of EC-SOD in VSMCs, leading to increased oxidative stress in the vascular wall. Taurine restores the secretion and expression of EC-SOD by ameliorating ER stress induced by homocysteine.

Key Words: atherosclerosis • antioxidants • vasculature • risk factors

This article has been cited by other articles:

				M. Kerkeni, F. Added, M. B. Farhat, A. Miled, F. Trivin, and K. Maaroufi Hyperhomocysteinaemia and parameters of antioxidative defence in Tunisian patients with coronary heart disease Ann Clin Biochem, March 1, 2008; 45(2): 193 - 198. [Abstract] [Full Text] [PDF]

				W. J. Welch, T. Chabrashvili, G. Solis, Y. Chen, P. S. Gill, S. Aslam, X. Wang, H. Ji, K. Sandberg, P. Jose, et al. Role of Extracellular Superoxide Dismutase in the Mouse Angiotensin Slow Pressor Response Hypertension, November 1, 2006; 48(5): 934 - 941. [Abstract] [Full Text] [PDF]

				D. BONSCH, K. BAYERLEIN, U. REULBACH, R. FISZER, T. HILLEMACHER, W. SPERLING, J. KORNHUBER, and S. BLEICH DIFFERENT ALLELE-DISTRIBUTION OF MTHFR 677 C -> T AND MTHFR -393 C -> A IN PATIENTS CLASSIFIED ACCORDING TO SUBTYPES OF LESCH'S TYPOLOGY Alcohol Alcohol., July 1, 2006; 41(4): 364 - 367. [Abstract] [Full Text] [PDF]

				A. Faggiano, D. Melis, R. Alfieri, M. De Martino, M. Filippella, F. Milone, G. Lombardi, A. Colao, and R. Pivonello Sulfur Amino Acids in Cushing's Disease: Insight in Homocysteine and Taurine Levels in Patients with Active and Cured Disease J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6616 - 6622. [Abstract] [Full Text] [PDF]

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				F. M. Faraci and S. P. Didion Vascular Protection: Superoxide Dismutase Isoforms in the Vessel Wall Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1367 - 1373. [Abstract] [Full Text] [PDF]

				G. S. Hossain, J. V. van Thienen, G. H. Werstuck, J. Zhou, S. K. Sood, J. G. Dickhout, A. B. L. de Koning, D. Tang, D. Wu, E. Falk, et al. TDAG51 Is Induced by Homocysteine, Promotes Detachment-mediated Programmed Cell Death, and Contributes to the Development of Atherosclerosis in Hyperhomocysteinemia J. Biol. Chem., August 8, 2003; 278(32): 30317 - 30327. [Abstract] [Full Text] [PDF]

				F. M. Faraci Hyperhomocysteinemia: A Million Ways to Lose Control Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 371 - 373. [Full Text] [PDF]

				U. Landmesser and H. Drexler Toward Understanding of Extracellular Superoxide Dismutase Regulation in Atherosclerosis: A Novel Role of Uric Acid? Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1367 - 1368. [Full Text] [PDF]

				T. Fukai, R. J Folz, U. Landmesser, and D. G Harrison Extracellular superoxide dismutase and cardiovascular disease Cardiovasc Res, August 1, 2002; 55(2): 239 - 249. [Abstract] [Full Text] [PDF]