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

Jong-Soon Choi,Kwan Soo Hong,Juhyeok Kim,Eui-Soon Park,Tae-uk Ha,Jaerang Rho

doi:10.1038/emm.2013.67

Abstract

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.

Highlights

Apoptosis has an essential role in tissue homeostasis in various organisms and is activated by a number of cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and inflammatory responses.[1,2,3,4] The receptor-mediated and mitochondria-mediated pathways are two major distinct apoptotic pathways that are active in mammalian cells.[5]
The expression of T-cell death-associated gene 51 (TDAG51) is enhanced by oxidative stress TDAG51 is a known cellular stress-responsive gene;[11,13,14] we first examined whether TDAG51 expression is enhanced by oxidative stresses in a time- and concentrationdependent manner
We investigated the functional role of TDAG51 expression in oxidative stress-induced apoptotic cell death

Summary

Introduction

Apoptosis has an essential role in tissue homeostasis in various organisms and is activated by a number of cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and inflammatory responses.[1,2,3,4] The receptor-mediated (extrinsic) and mitochondria-mediated (intrinsic) pathways are two major distinct apoptotic pathways that are active in mammalian cells.[5]. Activated caspase-3 directly induces apoptotic cell death.[6] The mitochondria-mediated pathway is activated by several cellular stresses, including oxidative stress, ER stress, and growth factor depletion. Cellular stress induces release of cytochrome c from mitochondria, and the released cytochrome c binds to apoptotic protease activating factor-1 and caspase-9. This complex directly induces caspase-3 activation and subsequently activates apoptotic cell death.[7,8]

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