Ablation of aldehyde reductase aggravates carbon tetrachloride-induced acute hepatic injury involving oxidative stress and endoplasmic reticulum stress

Ryusuke Akihara, Takujiro Homma, Jaeyong Lee, Ken-Ichi Yamada, Satoshi Miyata, Junichi Fujii

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

Aldehyde reductase (Akr1a) has been reported to be involved in the biosynthesis of ascorbic acid (AsA) in the mouse liver. Because Akr1a is expressed at high levels in the liver, we aimed to investigate the role of Akr1a in liver homeostasis by employing a carbon tetrachloride (CCl4)-induced hepatotoxicity model. Akr1a-deficient (Akr1a−/−) and wild-type (WT) mice were injected intraperitoneally with CCl4 and the extent of hepatic injury in the acute phase was assessed. Liver damage was heavier in the Akr1a−/− mice than in the WT mice. Furthermore, severe hepatic steatosis was observed in the livers of Akr1a−/− mice compared to WT mice and was restored to the levels in WT mice by AsA supplementation. Since the presence or absence of AsA had no effect on the decrease in CYP2E1 activity after the CCl4 treatment, it appears that AsA plays a role in the process after the bioactivation of CCl4. Biomarkers for oxidative stress and ER stress were markedly increased in the livers of Akr1a−/− mice and were effectively suppressed by AsA supplementation. Based on these collective results, we conclude that Akr1a exerts a protective effect against CCl4-induced hepatic steatosis by replenishing AsA via its antioxidative properties.

元の言語英語
ページ(範囲)765-771
ページ数7
ジャーナルBiochemical and Biophysical Research Communications
478
発行部数2
DOI
出版物ステータス出版済み - 9 16 2016

Fingerprint

Aldehyde Reductase
Endoplasmic Reticulum Stress
Oxidative stress
Carbon Tetrachloride
Ablation
Liver
Ascorbic Acid
Oxidative Stress
Wounds and Injuries
Cytochrome P-450 CYP2E1
Biosynthesis
Biomarkers
Homeostasis

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Ablation of aldehyde reductase aggravates carbon tetrachloride-induced acute hepatic injury involving oxidative stress and endoplasmic reticulum stress. / Akihara, Ryusuke; Homma, Takujiro; Lee, Jaeyong; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi.

:: Biochemical and Biophysical Research Communications, 巻 478, 番号 2, 16.09.2016, p. 765-771.

研究成果: ジャーナルへの寄稿記事

@article{485bfe5ee80943caad83b55bf500a5c0,
title = "Ablation of aldehyde reductase aggravates carbon tetrachloride-induced acute hepatic injury involving oxidative stress and endoplasmic reticulum stress",
abstract = "Aldehyde reductase (Akr1a) has been reported to be involved in the biosynthesis of ascorbic acid (AsA) in the mouse liver. Because Akr1a is expressed at high levels in the liver, we aimed to investigate the role of Akr1a in liver homeostasis by employing a carbon tetrachloride (CCl4)-induced hepatotoxicity model. Akr1a-deficient (Akr1a−/−) and wild-type (WT) mice were injected intraperitoneally with CCl4 and the extent of hepatic injury in the acute phase was assessed. Liver damage was heavier in the Akr1a−/− mice than in the WT mice. Furthermore, severe hepatic steatosis was observed in the livers of Akr1a−/− mice compared to WT mice and was restored to the levels in WT mice by AsA supplementation. Since the presence or absence of AsA had no effect on the decrease in CYP2E1 activity after the CCl4 treatment, it appears that AsA plays a role in the process after the bioactivation of CCl4. Biomarkers for oxidative stress and ER stress were markedly increased in the livers of Akr1a−/− mice and were effectively suppressed by AsA supplementation. Based on these collective results, we conclude that Akr1a exerts a protective effect against CCl4-induced hepatic steatosis by replenishing AsA via its antioxidative properties.",
author = "Ryusuke Akihara and Takujiro Homma and Jaeyong Lee and Ken-Ichi Yamada and Satoshi Miyata and Junichi Fujii",
year = "2016",
month = "9",
day = "16",
doi = "10.1016/j.bbrc.2016.08.022",
language = "English",
volume = "478",
pages = "765--771",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Ablation of aldehyde reductase aggravates carbon tetrachloride-induced acute hepatic injury involving oxidative stress and endoplasmic reticulum stress

AU - Akihara, Ryusuke

AU - Homma, Takujiro

AU - Lee, Jaeyong

AU - Yamada, Ken-Ichi

AU - Miyata, Satoshi

AU - Fujii, Junichi

PY - 2016/9/16

Y1 - 2016/9/16

N2 - Aldehyde reductase (Akr1a) has been reported to be involved in the biosynthesis of ascorbic acid (AsA) in the mouse liver. Because Akr1a is expressed at high levels in the liver, we aimed to investigate the role of Akr1a in liver homeostasis by employing a carbon tetrachloride (CCl4)-induced hepatotoxicity model. Akr1a-deficient (Akr1a−/−) and wild-type (WT) mice were injected intraperitoneally with CCl4 and the extent of hepatic injury in the acute phase was assessed. Liver damage was heavier in the Akr1a−/− mice than in the WT mice. Furthermore, severe hepatic steatosis was observed in the livers of Akr1a−/− mice compared to WT mice and was restored to the levels in WT mice by AsA supplementation. Since the presence or absence of AsA had no effect on the decrease in CYP2E1 activity after the CCl4 treatment, it appears that AsA plays a role in the process after the bioactivation of CCl4. Biomarkers for oxidative stress and ER stress were markedly increased in the livers of Akr1a−/− mice and were effectively suppressed by AsA supplementation. Based on these collective results, we conclude that Akr1a exerts a protective effect against CCl4-induced hepatic steatosis by replenishing AsA via its antioxidative properties.

AB - Aldehyde reductase (Akr1a) has been reported to be involved in the biosynthesis of ascorbic acid (AsA) in the mouse liver. Because Akr1a is expressed at high levels in the liver, we aimed to investigate the role of Akr1a in liver homeostasis by employing a carbon tetrachloride (CCl4)-induced hepatotoxicity model. Akr1a-deficient (Akr1a−/−) and wild-type (WT) mice were injected intraperitoneally with CCl4 and the extent of hepatic injury in the acute phase was assessed. Liver damage was heavier in the Akr1a−/− mice than in the WT mice. Furthermore, severe hepatic steatosis was observed in the livers of Akr1a−/− mice compared to WT mice and was restored to the levels in WT mice by AsA supplementation. Since the presence or absence of AsA had no effect on the decrease in CYP2E1 activity after the CCl4 treatment, it appears that AsA plays a role in the process after the bioactivation of CCl4. Biomarkers for oxidative stress and ER stress were markedly increased in the livers of Akr1a−/− mice and were effectively suppressed by AsA supplementation. Based on these collective results, we conclude that Akr1a exerts a protective effect against CCl4-induced hepatic steatosis by replenishing AsA via its antioxidative properties.

UR - http://www.scopus.com/inward/record.url?scp=84995680360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995680360&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2016.08.022

DO - 10.1016/j.bbrc.2016.08.022

M3 - Article

VL - 478

SP - 765

EP - 771

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -