Heme oxygenase 1, nuclear factor E2-related factor 2, and nuclear factor κb are involved in hemin inhibition of type 2 cationic amino acid transporter expression and L-arginine transport in stimulated macrophages

Pei Shan Tsai, Chien Chuan Chen, Pei-Shan Tsai, Lin Cheng Yang, Wan Yu Huang, Chun Jen Huang

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Abstract

BACKGROUND: l-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and l-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB) were also investigated. METHODS: Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 μm), lipopolysaccharide plus hemin (5, 50, or 500 μm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 μm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed. RESULTS: Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-κB activation, CAT-2 expression, and l-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-κB activation, CAT-2 expression, and l-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin. CONCLUSIONS: HO-1 induction significantly inhibited CAT-2 expression and l-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-κB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and l-arginine transport.

Original languageEnglish
Pages (from-to)1201-1210
Number of pages10
JournalAnesthesiology
Volume105
Issue number6
DOIs
Publication statusPublished - Dec 2006

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Cationic Amino Acid Transporter 2
NF-E2-Related Factor 2
Hemin
Heme Oxygenase-1
Lipopolysaccharides
Arginine
Macrophages
Nitric Oxide Synthase Type II
Carbon Monoxide
Nitric Oxide
Hemoglobins

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

@article{620010e1721d4e3b9e1390f83a49cf71,
title = "Heme oxygenase 1, nuclear factor E2-related factor 2, and nuclear factor κb are involved in hemin inhibition of type 2 cationic amino acid transporter expression and L-arginine transport in stimulated macrophages",
abstract = "BACKGROUND: l-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and l-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB) were also investigated. METHODS: Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 μm), lipopolysaccharide plus hemin (5, 50, or 500 μm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 μm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed. RESULTS: Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-κB activation, CAT-2 expression, and l-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-κB activation, CAT-2 expression, and l-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin. CONCLUSIONS: HO-1 induction significantly inhibited CAT-2 expression and l-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-κB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and l-arginine transport.",
author = "Tsai, {Pei Shan} and Chen, {Chien Chuan} and Pei-Shan Tsai and Yang, {Lin Cheng} and Huang, {Wan Yu} and Huang, {Chun Jen}",
year = "2006",
month = "12",
doi = "10.1097/00000542-200612000-00020",
language = "English",
volume = "105",
pages = "1201--1210",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "6",

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TY - JOUR

T1 - Heme oxygenase 1, nuclear factor E2-related factor 2, and nuclear factor κb are involved in hemin inhibition of type 2 cationic amino acid transporter expression and L-arginine transport in stimulated macrophages

AU - Tsai, Pei Shan

AU - Chen, Chien Chuan

AU - Tsai, Pei-Shan

AU - Yang, Lin Cheng

AU - Huang, Wan Yu

AU - Huang, Chun Jen

PY - 2006/12

Y1 - 2006/12

N2 - BACKGROUND: l-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and l-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB) were also investigated. METHODS: Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 μm), lipopolysaccharide plus hemin (5, 50, or 500 μm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 μm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed. RESULTS: Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-κB activation, CAT-2 expression, and l-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-κB activation, CAT-2 expression, and l-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin. CONCLUSIONS: HO-1 induction significantly inhibited CAT-2 expression and l-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-κB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and l-arginine transport.

AB - BACKGROUND: l-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and l-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB) were also investigated. METHODS: Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 μm), lipopolysaccharide plus hemin (5, 50, or 500 μm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 μm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed. RESULTS: Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-κB activation, CAT-2 expression, and l-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-κB activation, CAT-2 expression, and l-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin. CONCLUSIONS: HO-1 induction significantly inhibited CAT-2 expression and l-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-κB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and l-arginine transport.

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DO - 10.1097/00000542-200612000-00020

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VL - 105

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