Ethanol‐Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of <i>Aldh2</i> Knockout Mice

Kim, Yong‐Dae; Eom, Sang‐Yong; Ogawa, Masanori; Oyama, Tsunehiro; Isse, Toyohi; Kang, Jeong Woo; Zhang, Yan Wei; Kawamoto, Toshihiro; Kim, Heon

doi:10.1539/joh.49.363

Cited by 26 publications

(10 citation statements)

References 28 publications

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“…8‐OHdG is one of the predominant forms of free radical‐induced oxidative lesions, and has been widely used as a biomarker for oxidative stress . Previous studies have shown that ethanol induce the elevation of 8‐OHdG in mouse liver, and alcohol‐dependent individual serum . A variety of enzymatic and non‐enzymatic mechanisms have evolved to protect cells against ROS, including SOD .…”

Section: Discussionmentioning

confidence: 99%

Carvedilol improves ethanol‐induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats

Hakucho

Liu

et al. 2013

Hepatology Research

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Section: Discussionmentioning

confidence: 99%

Carvedilol improves ethanol‐induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats

Hakucho

Liu

et al. 2013

Hepatology Research

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“…Heavy and frequent alcohol consumption is one of the major risk factors for the development of ESCC (Yokoyama et al, ; Lee et al, ). Alcohol‐induced cellular injury is mainly mediated by the generation of ROS during ethanol metabolism (Albano, ; Kim et al, ), which leads to oxidative stress (Schuller et al, ; Koch et al, ). We show that ethanol upregulates expression of HO‐1 accompanied by activated p38MAPK and mTOR.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of HO‐1 is accompanied by activation of p38MAPK and mTOR in human oesophageal squamous carcinoma cells

Xiao²,

et al. 2013

Cell Biology International

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Induction of HO-1 protein can have both beneficial and detrimental effects for cells, including regulating proliferation and apoptosis of several tumours. We have investigated the regulation of HO-1, p38MAPK and mTOR in the context of proliferation, cell cycle events and apoptosis of oesophageal squamous cell carcinoma cells. Real-time PCR and Western blots were used to determine the expression levels of HO-1, p38MAPK, p-p38MAPK and p-mTOR. MTT assays were used to measure proliferation, FACS for cell cycle events and Annexin V staining for apoptosis. Proliferation of Eca109 cells was inhibited and apoptosis was induced in the presence of p38MAPK inhibitor (SB203580) and mTOR inhibitor (Rapamycin, RAPA). HO-1 expression was downregulated in cells treated with SB203580 and RAPA. HO-1 overexpression inhibited apoptosis and induced G2/M arrest in SB203580 and RAPA-treated cells. HO-1 expression was upregulated in the presence of ethanol, and was accompanied by activation of p38MAPK and mTOR. However, ethanol-treated cells exposed to HO-1 inhibitor showed no effect on p38MAPK and mTOR activation. The data suggest that ethanol-induced upregulation of HO-1 in oesophageal squamous cell carcinoma is accompanied by the activation of the p38MAPK and mTOR pathways.

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“…ALDH2 also appears to influence bone growth and cardiac function, as demonstrated by reductions in trabecular bone formation and cardiomyocyte function in Aldh2 −/− mice treated with alcohol [66, 67]. Stomach DNA adducts are dramatically increased after chronic ethanol feeding of Aldh2 −/− mice [68, 69] and acute ethanol treatment increases hepatic oxidative DNA adducts in null mice [70, 71]. The Aldh2 −/− strain represents a valuable strain that can be used to identify functions of ALDH2 in ethanol metabolism and toxicity.…”

Section: Mouse Models With Genetic Deficiencies In Acetaldehyde-mmentioning

confidence: 99%

Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer

Heit

Dong

Chen

et al. 2014

Advances in Experimental Medicine and Biology

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Alcohol abuse leads to tissue damage including a variety of cancers; however, the molecular mechanisms by which this damage occurs remains to be fully understood. The primary enzymes involved in ethanol metabolism include alcohol dehydrogenase (ADH), cytochrome P450 isoform 2E1, (CYP2E1), catalase (CAT), and aldehyde dehydrogenases (ALDH). Genetic polymorphisms in human genes encoding these enzymes are associated with increased risks of alcohol-related tissue damage, as well as differences in alcohol consumption and dependence. Oxidative stress resulting from ethanol oxidation is one established pathogenic event in alcohol-induced toxicity. Ethanol metabolism generates free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has been associated with diminished glutathione (GSH) levels as well as changes in other antioxidant mechanisms. In addition, the formation of protein and DNA adducts associated with the accumulation of ethanol-derived aldehydes can adversely affect critical biological functions and thereby promote cellular and tissue pathology. Animal models have proven to be valuable tools for investigating mechanisms underlying pathogenesis caused by alcohol. In this review, we provide a brief discussion on several animal models with genetic defects in alcohol metabolizing enzymes and GSH synthesizing enzymes and their relevance to alcohol research.

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Ethanol‐Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice

Cited by 26 publications

References 28 publications

Carvedilol improves ethanol‐induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats

Carvedilol improves ethanol‐induced liver injury via modifying the interaction between oxidative stress and sympathetic hyperactivity in rats

Upregulation of HO‐1 is accompanied by activation of p38MAPK and mTOR in human oesophageal squamous carcinoma cells

Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer

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