title: Ephedrine induced thioredoxin-1 expression through β-adrenergic receptor/cyclic AMP/protein kinase A/dopamine- and cyclic AMP-regulated phosphoprotein signaling pathway.
abstract: Ephedrine (Eph) is one of alkaloids that has been isolated from the ancient herb ephedra (ma huang) and is used as the treatment of asthma, hypotension and fatigue. However, its molecular mechanism remains unknown. Thioredoxin-1 (Trx-1) is a redox regulating protein, which has various biological activities, including regulating transcription factor DNA binding activity and neuroprotection. In this study, we found that Eph induced Trx-1 expression, which was inhibited by propranolol (β-adrenergic receptor inhibitor), but not by phenoxybenzamine (α-adrenergic receptor inhibitor) in rat pheochromocytoma PC12 cells. Moreover, the increase of Trx-1 expression was inhibited by SQ22536 (adenylyl cyclase inhibitor) and H-89 (protein kinase A inhibitor). Interestingly, the effect of Eph on dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) was similar to Trx-1. Thus, the relationship between Trx-1 and DARPP-32 was further studied. The DARPP-32 siRNA significantly reduced Trx-1 expression, but Trx-1 siRNA did not exchange DARPP-32. These results suggested that Eph induced the Trx-1 expression through β-adrenergic receptor/cyclic AMP/PKA/DARPP-32 signaling pathway. Furthermore, Eph induced PKA-mediated cyclic AMP response element-binding protein (CREB) phosphorylation. Down-regulation of DARPP-32 expression decreased phosphorylated CREB. In addition, Eph had a significant effect on the viability of the rat pheochromocytoma PC12 cells through β-adrenergic receptors. Trx-1 may play an important role in the actions of Eph.
authors: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
authors: Jin-Jing
authors: JJ
authors: Jia
authors: Xian-Si
authors: XS
authors: Zeng
authors: Ye
authors: Y
authors: Li
authors: Sha
authors: S
authors: Ma
authors: Jie
authors: J
authors: Bai
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004809:Ephedrine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D016716:PC12 Cells; D010643:Phenoxybenzamine / Q000494:pharmacology; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D007546:Isoquinolines; C497930:Ppp1r1b protein, rat; D034741:RNA, Small Interfering; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; D010643:Phenoxybenzamine; D013879:Thioredoxins; D011433:Propranolol; D000242:Cyclic AMP; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D004809:Ephedrine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D004298:Dopamine