title: Effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine-induced cytotoxicity in PC12 cells.
abstract: This study investigated the effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in rat adrenal pheochromocytoma (PC12) cells. Treatment with asarinin (25-50 μM) increased intracellular dopamine levels and enhanced L-DOPA-induced increases in dopamine levels. Asarinin (25 μM) induced cyclic AMP-dependent protein kinase A (PKA) signaling, leading to increased cyclic AMP-response element binding protein (CREB) and tyrosine hydroxylase (TH) phosphorylation, which in turn stimulated dopamine production. Asarinin (25 μM) also activated transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Bad phosphorylation at Ser 112, both of which have been shown to promote cell survival. In contrast, asarinin (25 μM) inhibited sustained ERK1/2, Bax, c-Jun N-terminal kinase (JNK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and caspase-3 activity, which were induced by 6-OHDA (100 μM). These results suggest that asarinin induces dopamine biosynthesis via activation of the PKA-CREB-TH system and protects against 6-OHDA-induced cytotoxicity by inhibiting the sustained activation of the ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea.
authors.forename: Kyung Sook
authors.initials: KS
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Zhao
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea. myklee@chungbuk.ac.kr.
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D030023:Asarum / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004149:Dioxoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004149:Dioxoles; D017705:Lignans; D016627:Oxidopamine; C054125:sesamin; D004298:Dopamine
keywords: 6-Hydroxydopamine; Asarinin; Cytotoxicity; Dopamine; ERK1/2; PC12