Ethanol-induced Stress Leads to Apoptosis Via Endoplasmic Reticulum Stress in SK-Hep1 Cells
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- OTA Michi
- Department of Pharmacology, Showa University School of Medicine
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- TSUJI Mayumi
- Department of Pharmacology, Showa University School of Medicine
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- MOCHIZUKI Yoshiya
- Department of Pharmacology, Showa University School of Medicine
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- INAGAKI Manami
- Department of Pharmacology, Showa University School of Medicine
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- MURAYAMA Mai
- Department of Pharmacology, Showa University School of Medicine
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- EMORI Haruka
- Department of Pharmacology, Showa University School of Medicine
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- SANBE Takehiko
- Department of Pharmacology, Showa University School of Medicine
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- OGUCHI Katsuji
- Department of Pharmacology, Showa University School of Medicine
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抄録
Alcoholic liver disease causes oxidative stress and induces apoptosis during alcohol metabolism. Ethanol causes endoplasmic reticulum (ER) stress in hepatocytes, stimulating the unfolded protein response (UPR) pathway and/or Ca2+-dependent calpain and caspase-4 activities. However, it is poorly understood whether ethanol-induced oxidative stress directly leads to apoptosis promoted by ER stress-associated pathways. This study investigated this question in human liver adenocarcinoma (SK-Hep1) cells, which were treated with 200 mM ethanol for 5 hours in the presence or absence of the antioxidant N-acetyl-cysteine (NAC). We found that treatment with ethanol significantly increased ROS production and cellular apoptosis in the SK-Hep1 cells, and that this response was significantly suppressed by pretreatment with NAC. Furthermore, pretreatment with NAC significantly reduced the observed increases in the mRNA expressions of Bip, Chop, and sXbp-1, and the activity of caspase-3 in ethanol-induced apoptotic cells. However, pretreatment with NAC did not attenuate the transient rise in cytosolic Ca2+ nor the activities of caspase-4 and calpain induced by ethanol. Together, these results revealed that ethanol-induced stress promotes apoptosis not only through mitochondria-mediated pathways, but also via ER stress. The findings further suggested that ethanol-induced oxidative stress and non-oxidative stress both stimulate the pathway regulating ER stress-mediated apoptosis.
収録刊行物
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- The Showa University Journal of Medical Sciences
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The Showa University Journal of Medical Sciences 23 (1), 23-35, 2011
昭和大学学士会
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詳細情報 詳細情報について
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- CRID
- 1390001204373053184
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- NII論文ID
- 130004841506
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- NII書誌ID
- AA10781651
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- COI
- 1:CAS:528:DC%2BC3MXhsFSkur7L
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- ISSN
- 21850968
- 09156380
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- 本文言語コード
- en
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- データソース種別
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- JaLC
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