Molecular biology of stress-elicited induction of catecholamine biosynthetic enzymes.
Immobilization stress elevates adrenal mRNA for several catecholamine biosynthetic enzymes. Phenylethanolamine N-methyltransferase (PNMT) mRNA is elevated in response to as little as 5 minutes of immobilization, which appears to be a direct consequence of the large rise of glucocorticoids. Tyrosine hydroxylase (TH) mRNA levels are not elevated under these conditions, but are maximally induced by 30 min of a single immobilization. Dopamine beta-hydroxylase (DBH) requires repeated stress for maximal induction. Transcriptional inhibitor actinomycin D prevented the elevation of TH and PNMT mRNA with a single immobilization. Oligonucleotides corresponding to the AP-1 like element in the TH promoter and an important regulatory element in the DBH promoter were used in binding assays with adrenomedullary extracts of rats exposed to stress. The complexes were UV cross-linked and analyzed by gel electrophoresis. The complex bound to the TH AP-1 site contained c-fos and other proteins (including cJun). The complex to the DBH-1 element contained several proteins, probably including fos related proteins but lacked c-fos. Immunoblots found that c-fos is induced in the adrenal medulla near maximally by one hour immobilization and cJun and JunD are present in higher constitutive levels and are only moderately regulated by immobilization stress. The results indicate that different mechanisms of transcriptional activation are used by several members of the catecholamine biosynthetic pathway.
Sabban
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EL
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
Hiremagalur
B
B
Nankova
B
B
Kvetnanský
R
R
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D017781:Genes, Immediate-Early; D008297:Male; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D002395:Catecholamines; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase