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Link Between ER‐Stress, PPAR‐Alpha Activation, and BET Inhibition in Relation to Apolipoprotein A‐I Transcription in HepG2 Cells
Author(s) -
van der Krieken Sophie E.,
Popeijus Herman E.,
Mensink Ronald P.,
Plat Jogchum
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25858
Subject(s) - transcription factor , transcription (linguistics) , alpha (finance) , chemistry , apolipoprotein b , peroxisome proliferator activated receptor , microbiology and biotechnology , biology , receptor , biochemistry , medicine , gene , philosophy , cholesterol , linguistics , construct validity , nursing , patient satisfaction
Activating transcription factor peroxisome proliferator‐activated receptor alpha (PPARα) may increase apoA‐I transcription. Furthermore, Bromodomain and Extra‐Terminal domain (BET) protein inhibitors increase, whereas Endoplasmic Reticulum (ER) stress decreases apoA‐I transcription. We examined possible links between these processes as related to apoA‐I transcription in HepG2 cells. JQ1(+), thapsigargin, and GW7647 were used to induce, respectively BET inhibition, ER‐stress, and PPARα activation. Expression of ER‐stress markers (CHOP, XBP1s) was analyzed by western blotting. PPARα, KEAP1 (marker for BET inhibition), and apoA‐I mRNAs were measured using qPCR. ER‐stress and BET inhibition both decreased PPARα mRNA expression and activity, but did not interfere with each other, as ER‐stress did not change KEAP1 and JQ1(+) did not influence ER‐stress marker production. Interestingly, PPARα activation and BET‐inhibition diminished ER‐stress marker production and rescued apoA‐I transcription during existing ER‐stress. We conclude that the ER‐stress mediated reduction in apoA‐I transcription could be partly mediated via the inhibition of PPARα mRNA expression and activity. In addition, BET inhibition increased apoA‐I transcription, even if PPARα production and activity were decreased. Finally, both BET inhibition and PPARα activation ameliorate the apoA‐I lowering effect of ER‐stress and are therefore interesting targets to elevate apoA‐I transcription. J. Cell. Biochem. 118:2161–2167, 2017. © 2016 Wiley Periodicals, Inc.