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1. Contents Vol. 37, 2013

Author

Siddik Momin Adam, Cheryl Gilmartin, Maurizio Gallieni, Pinar Ergin, Yu Pei, Min Huang, Ayelet Grupper, Ercan Ok, Umasankar Mathuram Thiyagarajan, Moshe Shashar, Diego Brancaccio, A. Oliet, Ajay K. Singh, M.L. Illescas, Mehmet Ozkahya, Usasiri Srisakul, Timur Köse, E. Chen, Zhen Zhao, Gulay Asci, Xianglan Huang, Xue Zhang, G. Fernández-Juárez, F. Rivera, Peter A. McCullough, J. Baltar, Longshan Liu, Yuichi Masuda, P. García-Frías, Jula K. Inrig, Hassan N. Ibrahim, Qian Fu, Jessica Kendrick, Shailendra Sharma, Naim Issa, Shelly Sapp, Ou Wang, Rui Zhang, Jing Sun, M. Sierra, Ohad Ben Tur, M. Praga, J. Ballarín, Soner Duman, Jun Yuan, Sanjeev Akkina, Weibo Xia, Yael Pri-Paz, Druck Reinhardt Druck Basel, Shuman Liu, Vittorio E. Andreucci, Meltem Sezis Demirci, Kim McFann, E. Mérida, Huseyin Toz, Hirohito Ichii, Gil Chernin, E. López-Rubio, Yanfeng Liu, Aleksandra Kukla, Nosratola D. Vaziri, Jose A.L. Arruda, Michel Chonchol, Yaping Liu, R. Poveda, Xiaoping Xing, Wei Yang, Yan Jiang, Dganit Bahry, Ian H. de Boer, Silvio Bertoli, Amirthavarshini Ponnuswamy, Nuo Si, Huiman X. Barnhart, Anna C. Porter, Lynda A. Szczech, Luca Neri, Donal N. Reddan, J. Lucas, Changxi Wang, Jun Li, Lisa A. Rocca Rey, C. Ramos, M.A. Frutos, Satz Mengensatzproduktion, Mei Li, J. Fulladosa, Tamara Chernichovski, Sharon Levi, A. Vigil, A. Segarra, Taskin Colak, Atul Bagul, Mahyar Khazaeli, Cenk Demirci, Uptal D. Patel, Idit F. Schwartz, Robert M. Califf, and Jiawen Huang

Subjects
Gerontology, Nephrology, business.industry, Library science, Medicine, business
Published
2013

2. Cyclosporine attenuates arginine transport, in human endothelial cells, through modulation of cationic amino acid transporter-1

Author

Yael Pri-Paz, Dganit Bahry, Moshe Shashar, Gil Chernin, Ayelet Grupper, Tamara Chernichovski, Sharon Levi, Idit F. Schwartz, and Ohad Ben Tur

Subjects
Protein Kinase C-alpha, Arginine, Nitric Oxide Synthase Type III, Pharmacology, Nitric Oxide, Nitric oxide, chemistry.chemical_compound, medicine, Human Umbilical Vein Endothelial Cells, Humans, Endothelial dysfunction, Protein kinase A, Nitrites, Cationic Amino Acid Transporter 1, Arginine transport, Nitrates, business.industry, Endothelial Cells, Biological Transport, medicine.disease, Endothelial stem cell, chemistry, Biochemistry, Nephrology, Cyclosporine, Human umbilical vein endothelial cell, business, Peroxynitrite, Immunosuppressive Agents
Abstract

Background: The spectrum of cardiovascular toxicity by cyclosporine (CsA) includes hypertension, accelerated atherosclerosis, and thrombotic microangiopathy, all of which are the result of endothelial cell dysfunction. Endothelial cell dysfunction is characterized by decreased endothelial nitric oxide synthase (eNOS) activity. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. CsA has been shown to attenuate nitric oxide (NO) generation. However, the mechanism remains elusive. We hypothesize that CsA inhibits eNOS activity through modulation of its selective arginine supplier CAT-1. Methods: We studied the effect of CsA on arginine uptake, NO2/NO3 generation, and CAT-1, protein kinase Cα (PKCα), and phosphorylated PKCα protein expression in human umbilical vein endothelial cell cultures (HUVEC) in the absence and presence of L-arginine. Results: CsA (0.5-2 μg/ml) significantly attenuated arginine transport in a dose- and time-dependent manner, a phenomenon which was prevented by co-incubation with L-arginine (1 mM). The aforementioned findings were accompanied by increased protein nitration, a measure for peroxynitrite accumulation. In contrast, no changes were observed in NO2/NO3 generation. CsA significantly decreased the abundance of CAT-1 protein, an effect that was attenuated by L-arginine. PKCα and phosphorylated PKCα (CAT-1 inhibitors) protein contents were not affected by CsA. Conclusion: CsA inhibits arginine transport and induces protein nitration in HUVEC through modulation of CAT-1.

Published
2013

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