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Title: Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC

Abstract

Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor {alpha}.

Authors:
 [1];  [2];  [3];  [3];  [1];  [1];  [1];  [1];  [1];  [3];  [1]
  1. Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550 (Japan)
  2. Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550 (Japan). E-mail: ryuichi@med.nagoya-u.ac.jp
  3. Department of Endocrinology and Metabolism, Division of Molecular and Cellular Adaptation, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)
Publication Date:
OSTI Identifier:
20798850
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 341; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2006.01.052; PII: S0006-291X(06)00131-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMP; CARBOXYLASE; ENDOTHELIUM; INCUBATION; INFLAMMATION; LIPIDS; NITRIC OXIDE; PHOSPHORYLATION; RECEPTORS; VEINS

Citation Formats

Murakami, Hisashi, Murakami, Ryuichiro, Kambe, Fukushi, Cao, Xia, Takahashi, Ryotaro, Asai, Toru, Hirai, Toshihisa, Numaguchi, Yasushi, Okumura, Kenji, Seo, Hisao, and Murohara, Toyoaki. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.01.052.
Murakami, Hisashi, Murakami, Ryuichiro, Kambe, Fukushi, Cao, Xia, Takahashi, Ryotaro, Asai, Toru, Hirai, Toshihisa, Numaguchi, Yasushi, Okumura, Kenji, Seo, Hisao, & Murohara, Toyoaki. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC. United States. doi:10.1016/j.bbrc.2006.01.052.
Murakami, Hisashi, Murakami, Ryuichiro, Kambe, Fukushi, Cao, Xia, Takahashi, Ryotaro, Asai, Toru, Hirai, Toshihisa, Numaguchi, Yasushi, Okumura, Kenji, Seo, Hisao, and Murohara, Toyoaki. Fri . "Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC". United States. doi:10.1016/j.bbrc.2006.01.052.
@article{osti_20798850,
title = {Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC},
author = {Murakami, Hisashi and Murakami, Ryuichiro and Kambe, Fukushi and Cao, Xia and Takahashi, Ryotaro and Asai, Toru and Hirai, Toshihisa and Numaguchi, Yasushi and Okumura, Kenji and Seo, Hisao and Murohara, Toyoaki},
abstractNote = {Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor {alpha}.},
doi = {10.1016/j.bbrc.2006.01.052},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 341,
place = {United States},
year = {Fri Mar 24 00:00:00 EST 2006},
month = {Fri Mar 24 00:00:00 EST 2006}
}