Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

Ishihara, Yasuhiro; Takemoto, Takuya; Itoh, Kouichi; Ishida, Atsuhiko; Yamazaki, Takeshi

doi:10.1074/jbc.m115.659151

Cited by 85 publications

(36 citation statements)

References 58 publications

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“…The adipocyte size was significantly larger in WAT of the Blvra FatKO as compared to Blvra Flox mice ( Figure 5C), but this was not observed in BAT ( Figure 5D). Also, Sod2 was significantly increased in WAT, indicating oxidative stress levels were high, which is known to be heightened by inflammatory stimuli [44]. Similar to the mitotracker staining, Cox2, a gene known to control mitochondria in WAT [45], was significantly reduced.…”

Section: Adipose Knockout Of Bvra Reduces Mitochondrial Number and Bementioning

confidence: 73%

Biliverdin Reductase A (BVRA) Knockout in Adipocytes Induces Hypertrophy and Reduces Mitochondria in White Fat of Obese Mice

et al. 2020

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Biliverdin reductase (BVR) is an enzymatic and signaling protein that has multifaceted roles in physiological systems. Despite the wealth of knowledge about BVR, no data exist regarding its actions in adipocytes. Here, we generated an adipose-specific deletion of biliverdin reductase-A (BVRA) (BlvraFatKO) in mice to determine the function of BVRA in adipocytes and how it may impact adipose tissue expansion. The BlvraFatKO and littermate control (BlvraFlox) mice were placed on a high-fat diet (HFD) for 12 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were quantitated at the end of the 12 weeks. The data showed that the percent body fat and body weights did not differ between the groups; however, BlvraFatKO mice had significantly higher visceral fat as compared to the BlvraFlox. The loss of adipocyte BVRA decreased the mitochondrial number in white adipose tissue (WAT), and increased inflammation and adipocyte size, but this was not observed in brown adipose tissue (BAT). There were genes significantly reduced in WAT that induce the browning effect such as Ppara and Adrb3, indicating that BVRA improves mitochondria function and beige-type white adipocytes. The BlvraFatKO mice also had significantly higher fasting blood glucose levels and no changes in plasma insulin levels, which is indicative of decreased insulin signaling in WAT, as evidenced by reduced levels of phosphorylated AKT (pAKT) and Glut4 mRNA. These results demonstrate the essential role of BVRA in WAT in insulin signaling and adipocyte hypertrophy.

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Section: Adipose Knockout Of Bvra Reduces Mitochondrial Number and Bementioning

confidence: 73%

Biliverdin Reductase A (BVRA) Knockout in Adipocytes Induces Hypertrophy and Reduces Mitochondria in White Fat of Obese Mice

et al. 2020

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“…(22) The percentage of lactate dehydrogenase activity in the medium was calculated by dividing the activity in the medium by the total (medium + lysate) activity and expressed as the percent lactate dehydrogenase release.…”

Section: Methodsmentioning

confidence: 99%

Involvement of reactive oxygen species derived from mitochondria in neuronal injury elicited by methylmercury

Ishihara

Tsuji

Kawamoto

et al. 2016

J. Clin. Biochem. Nutr.

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Methylmercury induces oxidative stress and subsequent neuronal injury. However, the mechanism by which methylmercury elicits reactive oxygen species (ROS) production remains under debate. In this study, we investigated the involvement of mitochondrial ROS in methylmercury-induced neuronal cell injury using human neuroblastoma SH-SY5Y-derived ρ0 cells, which have a deletion of mitochondrial DNA and thus decreased respiratory activity. SH-SY5Y cells were cultured for 60 days in the presence of ethidium bromide to produce ρ0 cells. Our ρ0 cells showed decreases in the cytochrome c oxidase expression and activity as well as oxygen consumption compared with original SH-SY5Y cells. Methylmercury at a concentration of 1 µM induced cell death with oxidative stress in original SH-SY5Y cells, but not ρ0 cells, indicating that ρ0 cells are resistant to methylmercury-induced oxidative stress. ρ0 cells also showed tolerance against hydrogen peroxide and superoxide anion, suggesting that ρ0 cells are resistant to total ROS. These data indicate that mitochondrial ROS are clearly involved in oxidative stress and subsequent cell death induced by methylmercury. Considering that the dominant mechanism of ROS generation elicited by methylmercury is due to direct antioxidant enzyme inhibition, mitochondria might play a role in amplifying ROS in methylmercury-induced neurotoxicity.

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“…mRNA levels were determined according to our previous report [13]. The primer sequences are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Suppressive effects of aryl-hydrocarbon receptor repressor on adipocyte differentiation in 3T3-L1 cells

Ishihara

Tsuji

Vogel

2018

Archives of Biochemistry and Biophysics

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The aryl-hydrocarbon receptor repressor (AhRR) negatively regulates aryl-hydrocarbon receptor (AhR) signaling via its inhibitory transactivation. AhR is well known to suppress adipocyte differentiation, but the function of AhRR during adipogenesis is unclear. The purpose of this study was to investigate the role of AhRR in adipocyte differentiation using 3T3-L1 cells. During the early phase of differentiation, AhRR expression was transiently induced, but throughout the entire differentiation process, low levels of AhR expression were maintained. AhRR knockdown significantly increased not only glycerol-3-phosphate dehydrogenase (GPDH) activity but also lipid accumulation inside the cells. AhRR overexpression clearly reduced GPDH activity and lipid accumulation, indicating that AhRR upregulation during the early stage of adipogenesis suppresses adipocyte differentiation. Since AhRR knockdown increases the expression and activity of peroxisome proliferator-activated receptor γ(PPARγ), AhRR negatively regulates PPARγ during adipogenesis. In summary, similar to AhR, AhRR acts as an inhibitor of adipocyte differentiation. In addition to controlling the negative feedback loop of AhR, AhRR might be involved in other functions, especially in adipocyte differentiation processes.

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Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

Cited by 85 publications

References 58 publications

Biliverdin Reductase A (BVRA) Knockout in Adipocytes Induces Hypertrophy and Reduces Mitochondria in White Fat of Obese Mice

Biliverdin Reductase A (BVRA) Knockout in Adipocytes Induces Hypertrophy and Reduces Mitochondria in White Fat of Obese Mice

Involvement of reactive oxygen species derived from mitochondria in neuronal injury elicited by methylmercury

Suppressive effects of aryl-hydrocarbon receptor repressor on adipocyte differentiation in 3T3-L1 cells

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