Role of BI-1 (TEGT)-mediated ERK1/2 activation in mitochondria-mediated apoptosis and splenomegaly in BI-1 transgenic mice

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• 作者：Jung-Hyun Kim^a ; Eung-Ryoung Lee^a ; Kilsoo Jeon^a ; Hye Yeon Choi^a ; Hyejin Lim^a ; Su-Jeong Kim^a ; Han-Jung Chae^b ; Seung Hwa Park^c ; SangUk Kim^d ; Young Rok Seo^e ; Jin-Hoi Kim^a ; Ssang-Goo Cho^a ; ^{ssangoo@konkuk.ac.kr}
• 关键词：Bax inhibitor-1 ; BI-1 family protein ; ERK1/2 ; Splenomegaly ; Autoimmune response
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2012
• 期刊代码：20_01674889
• 类别：bio
• 出版时间：April, 2012
• 卷：1823
• 期：4
• 页码：876-888
• 文件大小：2246 K

摘要

Bax Inhibitor-1 (BI-1) is an evolutionally conserved apoptotic suppressor and belongs to the BI-1 family of proteins, which contain BI-1-like transmembrane domains. As their cellular functions and regulatory mechanisms remain incompletely understood, we compared their anti-apoptotic properties. Forced expression of BI-1 resulted in the most effective suppression of stress-induced apoptosis, compared with other family members, together with significant extracellular signal-regulated kinase (ERK)1/2 activation. BI-1-mediated ERK1/2 activation led to the suppression of mitochondria-mediated reactive oxygen species (ROS) production. Involvement of the ERK signaling pathway in BI-1-induced anti-apoptotic effects was confirmed by knockdown studies with ERK- or BI-1-specific siRNA. Moreover, we produced transgenic (TG) mice overexpressing BI-1, and the relationship between ERK1/2 activation and the suppression of ROS production or apoptosis was confirmed in mouse embryonic fibroblast (MEF) cells derived from these mice. Interestingly, we found that BI-1 TG mice showed splenomegaly and abnormal megakaryopoiesis. Taken together, our results suggest that BI-1-induced ERK1/2 activation plays an important role in the modulation of intracellular ROS generation and apoptotic cell death and may also affect autoimmune response.