Premium
ACTH/cAMP regulates the expression of acid ceramidase (ASAH1) in H295R human adrenocortical cells
Author(s) -
Lucki Natasha Chrystman,
Sewer Marion B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.807.1
Subject(s) - sphingosine , creb , endocrinology , medicine , biology , chromatin immunoprecipitation , gene expression , receptor , chemistry , microbiology and biotechnology , gene , transcription factor , biochemistry , promoter
Acid ceramidase (ASAH1) is a key enzyme for sphingolipid metabolism that regulates the amount of ceramide, sphingosine, and sphingosine‐1‐phosphate within the cell. Based on our previous studies demonstrating that sphingosine is an endogenous ligand for the nuclear receptor steroidogenic factor‐1 (SF‐1), we examined the role of adrenocorticotropin hormone (ACTH) signaling in regulating the expression of ASAH1. Using H295R adrenocortical cells, we show that ACTH/cAMP increases mRNA and reporter gene activity of ASAH1. Using chromatin immunoprecipitation and reporter gene assays, we have identified the glucocorticoid receptor (GR) and cAMP‐responsive element binding protein (CREB) as important activators of this gene. We propose that ACTH signaling promotes the recruitment of GR and CREB to the ASAH1 promoter and that this increase in ASAH1 gene expression regulates ligand availability and SF‐1 target expression in the human adrenal cortex.