Premium
C‐jun N‐terminal kinase regulates the interaction between 14‐3‐3 and Bad in ethanol‐induced cell death
Author(s) -
Han Jae Yoon,
Jeong Eun Young,
Kim Yoon Sook,
Roh Gu Seob,
Kim Hyun Joon,
Kang Sang Soo,
Cho Gyeong Jae,
Choi Wan Sung
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21759
Subject(s) - programmed cell death , ethanol , apoptosis , phosphorylation , kinase , c jun , microbiology and biotechnology , period (music) , protein kinase a , chemistry , cell , biology , biochemistry , transcription factor , gene , physics , acoustics
Activation of the c‐jun N‐terminal kinase (JNK) is known to be an important step during ethanol‐induced cell death, but it has yet to be identified how JNK regulates apoptosis. Therefore, we investigated the mechanism by which JNK induces cell death following ethanol treatment. Ethanol (6 g/kg, 20% in saline) was administered subcutaneously to postnatal 7 day rat pups. Twelve hours after the first ethanol administration, rat pups were decapitated, and extracts of total protein from cerebral cortices were prepared. Ethanol exposure induced phosphorylation of JNK but did not affect the expression levels of pro‐ and antiapoptotic proteins. Furthermore, interactions of phospho‐JNK (p‐JNK) with 14‐3‐3 as well as with Bad were enhanced in the cerebral cortices of ethanol‐treated rats. Pretreatment with JNK inhibitor (SP600125) of SH‐SY5Y cells inhibited JNK phosphorylation and interaction between p‐JNK and 14‐3‐3 resulting from ethanol. Furthermore, 14‐3‐3 interaction with Bad was diminished in the cerebral cortices of ethanol‐treated rats. These findings suggest that JNK induces Bad release from 14‐3‐3 by inhibiting their interaction. After this event, Bad binds to Bcl‐xL, releasing Bax from Bcl‐xL and leading to cell death. We hypothesize that JNK may play an important role during ethanol‐induced cell death via the inhibition of antiapoptotic function of 14‐3‐3 as well as activation of proapoptotic function of Bad. © 2008 Wiley‐Liss, Inc.