Transcriptional activation of the haem oxygenase-1 gene by cGMP via a cAMP response element/activator protein-1 element in primary cultures of rat hepatocytes.

摘要: The expression of the rate-limiting enzyme haem degradation, oxygenase-1 (HO-1), can be induced by various stimuli, including lipopolysaccharide, tumour necrosis factor alpha and NO. NO signal transmitted cGMP, therefore this study was aimed at testing activation HO-1 gene cGMP. In primary cultures rat hepatocytes, both mRNA protein were donor sodium nitroprusside 8-bromo-cGMP. induction cGMP prevented specific kinase G inhibitor KT5823. cGMP-dependent dose-dependent transcriptionally regulated, as determined studies with actinomycin D a nuclear run-on assay. Cycloheximide lowered to about one half. Luciferase reporter constructs driven 800 bp 5'-flanking region transiently transfected into hepatocytes; 8-bromo-cGMP caused 6-fold induction, which obliterated deletion mutation cAMP response element/activator protein-1 (CRE/AP-1) (-665/-654) site. Thus appears stimulated pathway may mediated mainly via CRE/AP-1 element in promoter.