Document Detail

Identification of two novel ACTH-responsive genes encoding manganese-dependent superoxide dismutase (SOD2) and the zinc finger protein TIS11b [tetradecanoyl phorbol acetate (TPA)-inducible sequence 11b].
MedLine Citation:
PMID:  12040026     Owner:  NLM     Status:  MEDLINE    
ACTH is the major trophic factor regulating and maintaining adrenocortical function, affecting such diverse processes as steroidogenesis, cell proliferation, cell migration, and cell survival. We used differential display RT-PCR to identify genes that are rapidly induced by ACTH in the bovine adrenal cortex. Of 42 PCR products differentially amplified from primary cultures of bovine adrenocortical cells treated with 10 nM ACTH, six identified mRNAs that were confirmed by Northern blot analysis to be induced by ACTH. Four of these amplicons encoded noninformative repetitive sequences. Of the other two sequenced amplicons, one encoded a partial sequence for mitochondrial manganese-dependent superoxide dismutase (SOD2), an enzyme that is likely to protect adrenocortical cells from the cytotoxic effects of radical oxygen species generated during steroid biosynthesis. The second was identified as TIS11b (phorbol-12-myristate-13-acetate-inducible sequence 11b)/ERF-1/cMG, a member of the CCCH double-zinc finger protein family. SOD2 induction by ACTH was independent of extracellular steroid concentration or oxidative stress. SOD2 and TIS11b mRNA expressions were rapidly induced by ACTH, reaching a maximal level after 8 h and 3 h of treatment, respectively. These ACTH effects were mimicked by forskolin but appeared independent of cortisol secretion. Upon ACTH treatment, induction of TIS11b expression closely followed the previously characterized peak of vascular endothelial growth factor (VEGF) expression. Transfection of a TIS11b expression plasmid into 3T3 fibroblasts induced a decrease in the expression of a reporter gene placed upstream of the VEGF 3'-untranslated region, indicating that TIS11b may be an important regulator of VEGF expression through interaction with its 3'-untranslated region.
Anna M Chinn; Delphine Ciais; Sabine Bailly; Edmond Chambaz; Jonathan LaMarre; Jean-Jacques Feige
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  16     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-31     Completed Date:  2003-01-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1417-27     Citation Subset:  IM    
INSERM EMI 01-05, Department of Molecular and Structural Biology, Commissariat à l'Energie Atomique, Grenoble, France F-38054.
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MeSH Terms
Adrenal Cortex / metabolism
Adrenocorticotropic Hormone / pharmacology*
Base Sequence
Cell Line
DNA-Binding Proteins*
Endothelial Growth Factors / metabolism
Gene Expression Regulation / drug effects*
Gene Expression Regulation, Enzymologic / drug effects
Immediate-Early Proteins / genetics*
Intercellular Signaling Peptides and Proteins / metabolism
Lymphokines / metabolism
Molecular Sequence Data
Organ Specificity
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Endothelial Growth Factors; 0/Immediate-Early Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Lymphokines; 0/RNA, Messenger; 0/Tristetraprolin; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 9002-60-2/Adrenocorticotropic Hormone

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