Senescence marker protein‐30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

Kondo, Yoshitaka; Masutomi, Hirofumi; Noda, Yoichi; Ozawa, Yusuke; Takahashi, Keita; Handa, Shizuo; Maruyama, Naoki; Shimizu, Takahiko; Ishigami, Akihito

doi:10.1016/j.fob.2014.05.003

Cited by 40 publications

(46 citation statements)

References 47 publications

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“…It is an active substance generated by living organisms, which can eliminate harmful materials such as free radicals produced during normal oxygen metabolism (28). It can react with oxygen free radicals to generate hydrogen peroxide (29); the latter is converted into water by the organism and excreted. Thus, SOD1 activity represents the free radical scavenging ability of the body.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Both SMP‐30‐knockout mice on a Lepr db/db background as well as SMP30/superoxide dismutase‐1 double‐knockout mice developed hepatic steatosis and presented higher levels of hepatic oxidative stress and superoxide anion radicals compared with WT mice. These findings were attributed to decreased levels of hepatic apolipoprotein B and transcription factors involved in lipid metabolism . Similarly, NASH induction by methionine and choline‐deficient diet into p53‐deficient male mice resulted in slower disease progression accompanied by lower ROS accumulation and lipid peroxidation as well as fewer apoptotic cells compared with the WT mice .…”

Section: The Role Of Senescence In Nafld/nashmentioning

confidence: 96%

The Role of Senescence in the Development of Nonalcoholic Fatty Liver Disease and Progression to Nonalcoholic Steatohepatitis

et al. 2019

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In recent years, cellular senescence has generated a lot of interest among researchers because of its involvement in both the normal aging process and common human diseases. During senescence, cells undergo alterations that include telomere shortening, nuclear area enlargement, and genomic and mitochondrial DNA damage, leading to irreversible cell cycle arrest, and secretion of proinflammatory cytokines. Evidence suggests that the complex process of senescence is involved in the development of a plethora of chronic diseases including metabolic and inflammatory disorders and tumorigenesis. Recently, several human and animal studies have emphasized the involvement of senescence in the pathogenesis and development of liver steatosis including the progression to nonalcoholic steatohepatitis (NASH) as characterized by the additional emergence of inflammation, hepatocyte ballooning, and liver fibrosis. The development of nonalcoholic fatty liver disease (NAFLD) and its progression to NASH are commonly accompanied by several pathophysiological events including metabolic dysregulation and inflammatory phenomena occurring within the liver that may contribute to or derive from cellular senescence, implying that the latter may be both a stimulus and a consequence of the disease. Conclusion: In this review, we summarize the current literature on the impact of cellular senescence in NAFLD/NASH and discuss the effectiveness and safety of novel senolytic drugs and therapeutic options available to delay or treat the disease. Finally, we identify the open questions and issues to be addressed in the near future.

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“…Original Article Superoxide dismutase is an antioxidant enzyme that changes superoxide anion radicals into hydrogen peroxide and molecular oxygen (22). With regard to lipid metabolism in the liver, it was shown that SOD1-knockout mice presented with increased lipid peroxidation and hepatic TG accumulation because of abnormal lipid metabolism in mouse liver (23).…”

mentioning

confidence: 99%

“…Furthermore, SOD-knockout mice hepatocytes included abnormally enlarged mitochondria (24). Kondo et al (22) reported that high levels of OS caused by defects in the antioxidant system as result of concomitant deficiency of SOD in SOD-knockout mice resulted in hepatic lipid accumulation via altered lipid metabolism.…”

mentioning

confidence: 99%

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease

Köroğlu

Canbakan²,

Atay³

et al. 2016

Turk J Gastroenterol

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Senescence marker protein‐30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

Cited by 40 publications

References 47 publications

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

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

The Role of Senescence in the Development of Nonalcoholic Fatty Liver Disease and Progression to Nonalcoholic Steatohepatitis

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease

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