Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L’Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

doi:10.1172/jci73957

Cited by 209 publications

(221 citation statements)

References 87 publications

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“…Oxidative stress is a crucial factor in the initiation and progression of HCC under various pathological conditions [48] . Oxidative stress can be induced by ROS produced in the mitochondria in non-alcoholic fatty liver disease, which damages hepatocytes, promotes pathologic polyploidization, triggers inflammation, and contributes to insulin resistance [49][50][51][52][53] . Additionally, oxidative stress is also involved in migration, invasion, and metastasis of HCC [54][55][56] .…”

Section: Hepatatocarcinogenesis and Oxidative Stressmentioning

confidence: 99%

Oxidative stress and hepatocarcinogenesis

Chung

2018

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. There are two major challenges for HCC, the first being that early detection is generally not applicable, and secondly, it is usually fatal within several months after diagnosis. HCC is an inflammation-induced cancer. It is known that chronic inflammation leads to oxidative/nitrosative stress and lipid peroxidation, generating excess oxidative stress, together with aldehydes which can react with DNA bases to form promutagenic DNA adducts. In this review, the evidence between oxidative stress and liver carcinogenesis is summarized. We focused on the potential of using DNA adducts as oxidative stress biomarkers for liver carcinogenesis.

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Section: Hepatatocarcinogenesis and Oxidative Stressmentioning

confidence: 99%

Oxidative stress and hepatocarcinogenesis

Chung

2018

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“…The pathogenic mechanism underlying NAFLD and its progression are not entirely understood. Accumulation of fat is an essential condition in the development of NAFLD (3), based on which hepatocyte oxidative stress starts causing injury to the liver, which accelerates the progression of NAFLD to more severe stages (4), such as non-alcoholic steatosis hepatitis, nonalcoholic fatty liver-related cirrhosis, and nonalcoholic fatty liver-related cancer (5). Oxidative stress (OS) is a condition of imbalance between the antioxidant defense mechanisms and the production of free radicals, which favors the latter, leading to potential damage (6).…”

Section: Introductionmentioning

confidence: 99%

Influence of different concentrations of uric acid on oxidative stress in steatosis hepatocytes

Cheng

Yang²,

Zhou

et al. 2018

Exp Ther Med

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Abstract. The development of nonalcoholic fatty liver disease (NAFLD) is caused by the steatosis of hepatocytes, which induces oxidative stress (OS). Thus, OS has an important role in the development of NAFLD. In the present study, the L-02 hepatocyte cell line was used to develop a steatosis cell model. The best model was determined using an MTT assay and the triglyceride levels. Model cells were treated with high concentrations of uric acid (UA; 0, 5, 10, 20 and 30 mg/dl) for 24, 48, 72 and 96 h. Indicators of oxidation were then measured, which included total superoxide dismutase (SOD), malonaldehyde (MDA) and reduced glutathione (GSH), and the transcriptional and translational levels of SOD1 and γ-glutamate-cysteine ligase (γ-GCLC) were also determined. In addition, the intracellular levels of aspartate aminotransferase and alanine aminotransferase (ALT) were detected. The activity of SOD1 decreased over time and the result was supported by the results of western blotting. The transcriptional levels of SOD1 in model cells was significantly higher than untreated cells at 48 h. With the decreased levels of SOD1 and GSH, MDA increased in a time-dependent manner. The content of GSH decreased with time as well, which was also reflected in the results of western blotting. The transcriptional levels of γ-GCLC in all UA-treated groups were lower when compared with those observed in the model group. The activity of ALT tended to increase, depending on the duration of treatment. Treatment with 5 and 10 mg/dl UA had an antioxidative effect on the model cells, and 30 mg/dl UA treatment for 48 h increased OS in the cells.

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“…It is also worth mentioning that a great proportion of hepatocytes, up to 85 % in rodents and about 35 % in humans, are polyploid cells, i.e., contain four (tetraploid) or eight (octoploid) sets of chromosomes in one or two nuclei [20]. Interestingly liver ploidy is known to be modified during injury and regeneration, including chronic human liver disease [21]. However, the physiological significance of liver ploidy and of its pathological alterations are still not completely understood, and this is an area of active research recently reviewed elsewhere [20,22].…”

Section: Introductionmentioning

confidence: 99%

Regulation of hepatocyte identity and quiescence

Berasain

Avila

2015

Cell. Mol. Life Sci.

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The liver is a highly differentiated organ with a central role in metabolism, detoxification and systemic homeostasis. To perform its multiple tasks, liver parenchymal cells, the hepatocytes, express a large complement of enabling genes defining their complex phenotype. This phenotype is progressively acquired during fetal development and needs to be maintained in adulthood to guarantee the individual's survival. Upon injury or loss of functional mass, the liver displays an extraordinary regenerative response, mainly based on the proliferation of hepatocytes which otherwise are long-lived quiescent cells. Increasing observations suggest that loss of hepatocellular differentiation and quiescence underlie liver malfunction in chronic liver disease and pave the way for hepatocellular carcinoma development. Here, we briefly review the essential mechanisms leading to the acquisition of liver maturity. We also identify the key molecular factors involved in the preservation of hepatocellular homeostasis and finally discuss potential strategies to preserve liver identity and function.

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Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Cited by 209 publications

References 87 publications

Oxidative stress and hepatocarcinogenesis

Oxidative stress and hepatocarcinogenesis

Influence of different concentrations of uric acid on oxidative stress in steatosis hepatocytes

Regulation of hepatocyte identity and quiescence

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