ABSTRACT
Angiotensin II- and K+-stimulated aldosterone production in the adrenocortical glomerulosa cells requires induction of the steroidogenic acute regulatory protein (StAR). While both agents activate Ca2+ signaling, the mechanisms leading to aldosterone synthesis are distinct, and the angiotensin II response cannot be mimicked by K+. We previously reported that StAR mRNA levels and promoter-reporter gene activity in transiently transfected H295R human adrenocortical cells were stimulated by angiotensin II but not by K+ treatment. The current study focused on identifying signaling pathways activated by angiotensin II that contribute to StAR transcriptional activation. We show that the angiotensin II-stimulated transcriptional activation of StAR was dependent upon influx of external calcium and requires protein kinase C activation. Furthermore we describe for the first time that the Janus tyrosine kinase family member, JAK2, was activated by angiotensin II treatment of H295R cells. Treatment of the cells with AG490, a selective inhibitor of JAK2, blocked JAK2 activation and StAR reporter gene activity and inhibited steroid production. Taken together these studies describe a novel pathway controlling StAR expression and steroidogenesis in adrenocortical cells.
Subject(s)
Adrenal Cortex/cytology , Angiotensin II/metabolism , Calcium/physiology , Phosphoproteins/metabolism , Protein-Tyrosine Kinases/physiology , Proto-Oncogene Proteins , Calcium/metabolism , Cell Line , Culture Media, Serum-Free/pharmacology , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Genes, Reporter , Humans , Immunoblotting , Janus Kinase 2 , Luciferases/metabolism , Progesterone/metabolism , Promoter Regions, Genetic , RNA, Messenger/metabolism , Radioimmunoassay , Signal Transduction , Time Factors , Transcription, Genetic , Transcriptional Activation , Transfection , Tyrphostins/pharmacologyABSTRACT
Zabon (Citrus maxima) is a large citrus fruit belonging to the Rutaceae family and containing a variety of psoralens including 5-methoxypsoralen. We describe the first case reports of a phytophotodermatitis caused by zabon.