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Differential Regulation of Bcl‐x L Gene Expression by Corticosterone, Progesterone, and Retinoic Acid
Author(s) -
Morrissy Steve J,
Sun Haipeng,
Zhang Jack,
Strom Joshua,
Chen Qin M.
Publication year - 2016
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21795
Subject(s) - retinoic acid , microbiology and biotechnology , messenger rna , apoptosis , transcription factor , chemistry , transcription (linguistics) , gene , electrophoretic mobility shift assay , biology , biochemistry , linguistics , philosophy
Corticosterone (CT), progesterone (PG), and retinoic acid (RA) are capable of inhibiting Doxorubicin (Dox) from inducing apoptosis in rat cardiomyocytes. Mechanistically, CT, PG, and RA induce increases of Bcl‐x L protein and mRNA, and activate a 3.2 kb bcl‐x gene promoter. CT and RA, but not PG, induced the activity of a 0.9 kb bcl‐x promoter, containing sequences for AP‐1 and NF‐kB binding. RA, but not CT or PG, induced NF‐kB activation. CT, but not PG or RA, induced AP‐1 activation, and induction of the 0.9 kb bcl‐x reporter by CT was inhibited by dominant negative c‐Jun TAM‐67 or removal of AP‐1 binding site. Therefore, although CT, PG, and RA all induce Bcl‐x L mRNA and protein, three independent mechanisms are in operation: while CT induces Bcl‐x L via AP‐1 transcription factor, and RA induces NF‐kB activation and bcl‐x promoter activity, PG induces Bcl‐x L via a mechanism independent of NF‐kB or AP‐1.