Signaling pathways of magnolol-induced adrenal steroidogensis.
This study focused on identifying the signalling mediating the effect of magnolol on corticosterone production. Magnolol-induced corticosterone production was completely inhibited by mitogen-activated protein kinase kinase (MEK)-inhibitor PD98059, tyrosine kinase (TK)-inhibitor genistein or Janus tyrosine kinase 2 (JAK2)-inhibitor AG490, suggesting that extracellular signal-regulated kinase (ERK) and JAK2 are both involved in this signaling cascade. Further, magnolol induced the transient phosphorylation of MEK, ERK, cAMP response-element binding protein (CREB) and the expression of 32 and 30 kDa steroidogenic acute regulatory protein (StAR) in a time-dependent manner. Inhibition of TK or JAK2 activities blocked magnolol-induced phosphorylation of MEK and ERK, again supporting the upstream role of JAK2. The activation of JAK2 or MEK apparently mediated the magnolol-induced phosphorylation of CREB and the upregulation of StAR. These findings demonstrate a novel pathway for magnolol to induce the expression of StAR, which regulates the rate-limiting step in sterodiogenesis.
Chen
Yung-Chia
YC
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei, Taiwan.
Chang
Ming-Fong
MF
Chen
Ying
Y
Wang
Seu-Mei
SM
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D053614:Janus Kinase 2; D017705:Lignans / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D000098682:Steroidogenic Acute Regulatory Protein
D001713:Biphenyl Compounds; D017362:Cyclic AMP Response Element-Binding Protein; D017705:Lignans; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D000098682:Steroidogenic Acute Regulatory Protein; C005498:magnolol; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D003345:Corticosterone