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Mol. Cells 2013; 36(4): 376-384

Published online October 31, 2013

https://doi.org/10.1007/s10059-013-0210-y

© The Korean Society for Molecular and Cellular Biology

S-Adenosyl Methionine Prevents Endothelial Dysfunction by Inducing Heme Oxygenase-1 in Vascular Endothelial Cells

Sun Young Kim, Seok Woo Hong, Mi-Ok Kim, Hyun-Sik Kim, Jung Eun Jang, Jaechan Leem, In-Sun Park, Ki-Up Lee, and Eun Hee Koh

1Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea, 2Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Korea, 3Department of Anatomy, College of Medicine, Inha University, Incheon 401-103, Korea, 4These authors contributed equally to this work.

Received: July 18, 2013; Revised: August 9, 2013; Accepted: August 12, 2013

Abstract

S-adenosyl methionine (SAM) is a key intermediate in the metabolism of sulfur amino acids and is a major methyl donor in the cell. Although the low plasma level of SAM has been associated with atherosclerosis, the effect of SAM administration on atherosclerosis is not known. Endothelial dysfunction is an early prerequisite for atherosclerosis. This study was undertaken to investigate the possible preventive effect of SAM on endothelial dysfunction and the molecular mechanism of its action. SAM treatment prevented endothelial dysfunction in high fat diet (HFD)-fed rats. In cultured human aortic endothelial cells, linoleic acid (LA) increased and SAM decreased cell apoptosis and endoplasmic reticulum stress. Both LA and SAM increased heme oxygenase-1 (HO-1) expression in an NF-E2-related factor 2-dependent manner. However, knoc-kdown of HO-1 reversed only the SAM-induced pre-ventive effect of cell apoptosis. The LA-induced HO-1 expression was dependent on PPAR?, whereas SAM in-duced HO-1 in a PPAR-independent manner. These data demonstrate that SAM treatment prevents endothelial dysfunction in HFD-fed animals by inducing HO-1 in vascular endothelial cells. In cultured endothelial cells, SAM-induced HO-1 was res-ponsible for the observed prevention of cell apoptosis. We propose that SAM treatment may represent a new therapeutic strategy for atherosclerosis.

Keywords endoplasmic reticulum stress, endothelial dysfunction, heme oxygenase-1, S-adenosyl methionine, vascular endothelial cell

Article

Research Article

Mol. Cells 2013; 36(4): 376-384

Published online October 31, 2013 https://doi.org/10.1007/s10059-013-0210-y

Copyright © The Korean Society for Molecular and Cellular Biology.

S-Adenosyl Methionine Prevents Endothelial Dysfunction by Inducing Heme Oxygenase-1 in Vascular Endothelial Cells

Sun Young Kim, Seok Woo Hong, Mi-Ok Kim, Hyun-Sik Kim, Jung Eun Jang, Jaechan Leem, In-Sun Park, Ki-Up Lee, and Eun Hee Koh

1Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 138-736, Korea, 2Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Korea, 3Department of Anatomy, College of Medicine, Inha University, Incheon 401-103, Korea, 4These authors contributed equally to this work.

Received: July 18, 2013; Revised: August 9, 2013; Accepted: August 12, 2013

Abstract

S-adenosyl methionine (SAM) is a key intermediate in the metabolism of sulfur amino acids and is a major methyl donor in the cell. Although the low plasma level of SAM has been associated with atherosclerosis, the effect of SAM administration on atherosclerosis is not known. Endothelial dysfunction is an early prerequisite for atherosclerosis. This study was undertaken to investigate the possible preventive effect of SAM on endothelial dysfunction and the molecular mechanism of its action. SAM treatment prevented endothelial dysfunction in high fat diet (HFD)-fed rats. In cultured human aortic endothelial cells, linoleic acid (LA) increased and SAM decreased cell apoptosis and endoplasmic reticulum stress. Both LA and SAM increased heme oxygenase-1 (HO-1) expression in an NF-E2-related factor 2-dependent manner. However, knoc-kdown of HO-1 reversed only the SAM-induced pre-ventive effect of cell apoptosis. The LA-induced HO-1 expression was dependent on PPAR?, whereas SAM in-duced HO-1 in a PPAR-independent manner. These data demonstrate that SAM treatment prevents endothelial dysfunction in HFD-fed animals by inducing HO-1 in vascular endothelial cells. In cultured endothelial cells, SAM-induced HO-1 was res-ponsible for the observed prevention of cell apoptosis. We propose that SAM treatment may represent a new therapeutic strategy for atherosclerosis.

Keywords: endoplasmic reticulum stress, endothelial dysfunction, heme oxygenase-1, S-adenosyl methionine, vascular endothelial cell

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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