Role of BI-1 (TEGT)-mediated ERK1/2 activation in mitochondria-mediated apoptosis and splenomegaly in BI-1 transgenic mice
SCIE
SCOPUS
- Title
- Role of BI-1 (TEGT)-mediated ERK1/2 activation in mitochondria-mediated apoptosis and splenomegaly in BI-1 transgenic mice
- Authors
- Kim, JH; Lee, ER; Jeon, K; Choi, HY; Lim, H; Kim, SJ; Chae, HJ; Park, SH; Kim, S; Seo, YR; Kim, JH; Cho, SG
- Date Issued
- 2012-04
- Publisher
- Elsevier
- Abstract
- 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 megakaiyopoiesis. Taken together, our results suggest that BM-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. (c) 2012 Elsevier B.V. All rights reserved.
- Keywords
- Bax inhibitor-1; BI-1 family protein; ERK1/2; Splenomegaly; Autoimmune response; INDUCED CELL-DEATH; ENDOPLASMIC-RETICULUM STRESS; SIGNAL-REGULATED KINASE; BAX INHIBITOR-1; OXIDATIVE STRESS; MAMMALIAN-CELLS; PROTEIN-KINASES; DOWN-REGULATION; PLANT HOMOLOG; MAP KINASE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/16719
- DOI
- 10.1016/J.BBAMCR.2012.01.016
- ISSN
- 0167-4889
- Article Type
- Article
- Citation
- Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1823, no. 4, page. 876 - 888, 2012-04
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