Several studies have recently demonstrated that G protein-coupled estrogen receptor (GPER) 30 directly binds to estrogen and mediates its action. The aim of the present study was to investigate the effects of GPER on cardiocyte apoptosis following ischemia/reperfusion injury (MIRI) in H9C2 myocardial cells. H9C2 cells were treated with a specific GPER agonist (G1), 17β-estradiol (E2) or the vehicle. The cells were subjected to 20 min of myocardial ischemia followed by 120 min of reperfusion. They were then randomly assigned to three experimental groups: Control, G1, E2. B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) levels were measured, Hoechst 33258 staining was performed to assess apoptosis, and superoxide dismutase (SOD), tumor necrosis factor (TNF)-α and adenosine triphosphatase (ATPase) levels were determined. To test the specificity of G1, GPER-knockout cells were treated with G1 and analyzed as stated above. Compared with the vehicle-treated groups, G1 and E2-treated groups exhibited elevated Bcl-2 levels, decreased Bax levels and cell apoptosis, significantly increased SOD and ATP levels and decreased TNF-α levels following ischemia-reperfusion. However, G1 had no evident effects on the GPER-knockout cells. In conclusion, the present study suggested that GPER activation provided a cardioprotective effect following ischemia-reperfusion by inhibiting cardiocyte apoptosis.

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Next to proinflammatory cytokines, autoimmunity has been identified as a key trigger for osteoclast activation and bone loss. IgG‐rheumatoid factor (IgG‐RF) immune complexes, which are present in patients with rheumatoid arthritis, were shown to boost osteoclast differentiation. To date, the regulation of IgG‐RF production in the absence of inflammatory triggers is unknown. Herein, we describe Fra1 as a key checkpoint that controls IgG‐RF production by plasma cells and regulates autoimmune‐mediated bone loss. Fra1 deficiency in B cells (Fra1ΔBcell) led to increased IgG1‐producing bone marrow plasma cells, enhanced IgG‐RF production, and increased bone loss associated with elevated osteoclast numbers after immunization. The effect of IgG‐RF on osteoclasts in vitro and on osteoclasts associated with bone loss in vivo was dependent on FcγR, especially FcγR3. Furthermore, immunization of WT mice with T‐cell‐dependent antigens induced a significant and robust decrease in Fra1 expression in bone marrow B cells, which was followed by increased IgG1 production and the induction of osteoclast‐mediated bone loss. Overall, these data identify Fra1 as a key mediator of IgG‐RF production and autoimmune‐mediated bone loss. © 2019 American Society for Bone and Mineral Research.

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.