T-Cell Death Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγ-RXRα Heterodimer Formation in Adipogenesis

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the master transcriptional regulator in adipogenesis. PPARγ forms a heterodimer with another nuclear receptor, retinoid X receptor (RXR), to form an active transcriptional complex, and their transcriptional activity is tightly regulated by the association with either coactivators or corepressors. In this study, we identified T-cell death-associated gene 51 (TDAG51) as a novel corepressor of PPARγ-mediated transcriptional regulation. We showed that TDAG51 expression is abundantly maintained in the early stage of adipogenic differentiation. Forced expression of TDAG51 inhibited adipocyte differentiation in 3T3-L1 cells. We found that TDAG51 physically interacts with PPARγ in a ligand-independent manner. In deletion mutant analyses, large portions of the TDAG51 domains, including the pleckstrin homology-like, glutamine repeat and proline-glutamine repeat domains but not the proline-histidine repeat domain, are involved in the interaction with the region between residues 140 and 506, including the DNA binding domain, hinge, ligand binding domain and activation function-2 domain, in PPARγ. The heterodimer formation of PPARγ-RXRα was competitively inhibited in a ligand-independent manner by TDAG51 binding to PPARγ. Thus, our data suggest that TDAG51, which could determine adipogenic cell fate, acts as a novel negative regulator of PPARγ by blocking RXRα recruitment to the PPARγ-RXRα heterodimer complex in adipogenesis.

Development of Portable Digital Radiography System with a Device for Monitoring X-ray Source-Detector Angle and Its Application in Chest Imaging.

This study developed a device measuring the X-ray source-detector angle (SDA) and evaluated the imaging performance for diagnosing chest images. The SDA device consisted of Arduino, an accelerometer and gyro sensor, and a Bluetooth module. The SDA values were compared with the values of a digital angle meter. The performance of the portable digital radiography (PDR) was evaluated using the signal-to-noise (SNR), contrast-to-noise ratio (CNR), spatial resolution, distortion and entrance surface dose (ESD). According to different angle degrees, five anatomical landmarks were assessed using a five-point scale. The mean SNR and CNR were 182.47 and 141.43. The spatial resolution and ESD were 3.17 lp/mm (157 µm) and 0.266 mGy. The angle values of the SDA device were not significantly difference as compared to those of the digital angle meter. In chest imaging, the SNR and CNR values were not significantly different according to the different angle degrees. The visibility scores of the border of the heart, the fifth rib and the scapula showed significant differences according to different angles (p < 0.05), whereas the scores of the clavicle and first rib were not significant. It is noticeable that the increase in the SDA degree was consistent with the increases of the distortion and visibility score. The proposed PDR with a SDA device would be useful for application in the clinical radiography setting according to the standard radiography guidelines.

TDAG51 deficiency promotes oxidative stress-induced apoptosis through the generation of reactive oxygen species in mouse embryonic fibroblasts.

Apoptosis has an important role in maintaining tissue homeostasis in cellular stress responses such as inflammation, endoplasmic reticulum stress, and oxidative stress. T-cell death-associated gene 51 (TDAG51) is a member of the pleckstrin homology-like domain family and was first identified as a pro-apoptotic gene in T-cell receptor-mediated cell death. However, its pro-apoptotic function remains controversial. In this study, we investigated the role of TDAG51 in oxidative stress-induced apoptotic cell death in mouse embryonic fibroblasts (MEFs). TDAG51 expression was highly increased by oxidative stress responses. In response to oxidative stress, the production of intracellular reactive oxygen species was significantly enhanced in TDAG51-deficient MEFs, resulting in the activation of caspase-3. Thus, TDAG51 deficiency promotes apoptotic cell death in MEFs, and these results indicate that TDAG51 has a protective role in oxidative stress-induced cell death in MEFs.