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

• Published in: Experimental & molecular medicine Vol. 45; no. 8; p. e35
• Main Authors: Park, Eui-Soon, Kim, Juhyeok, Ha, Tae-uk, Choi, Jong-Soon, Soo Hong, Kwan, Rho, Jaerang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2013; Springer Nature B.V; Nature Publishing Group
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Embryo, Mammalian - cytology; Fibroblasts - enzymology; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation; Intracellular Space - metabolism; Medical Biochemistry; Mice; Mitogen-Activated Protein Kinases - metabolism; Molecular Medicine; NF-kappa B - metabolism; Original; original-article; Oxidative Stress - genetics; Reactive Oxygen Species - metabolism; Signal Transduction; Stem Cells; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - metabolism; TDAG51; apoptosis; oxidative stress; ROS
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/emm.2013.67

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. Cell biology: Secrets of surviving stress Researchers in Korea have demonstrated how an enigmatic protein helps cells to survive stressful conditions. Cells produce chemicals known as reactive oxygen species (ROS) over the course of normal metabolism as well as in response to certain environmental triggers. Accumulation of ROS molecules is toxic, however, and can ultimately lead to cell death via a process called apoptosis. Previous studies have yielded findings suggesting that TDAG51 can either promote or prevent apoptosis. Jaerang Rho's group at Chungnam National University showed that the T cell death-associated gene 51 (TDAG51) protein helps to fight cellular stress by reducing ROS levels. They demonstrated that TDAG51-deficient cells produced greater levels of ROS and were more likely to subsequently undergo apoptosis than normal cells under stressful conditions. These results therefore suggest a protective role for TDAG51.