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Effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine-induced cytotoxicity in PC12 cells

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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.

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Acknowledgements

The authors appreciate financial support from the National Research Foundation of Korea (Grant No. 2013R1A1A2058230, 2015-2016), Republic of Korea.

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    1. College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea

      Hyun Jin Park, Kyung Sook Lee, Ting Ting Zhao, Kyung Eun Lee & Myung Koo Lee

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    1. Hyun Jin Park
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    Hyun Jin Park and Kyung Sook Lee have contributed equally to the study.

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    Park, H.J., Lee, K.S., Zhao, T.T. et al. Effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine-induced cytotoxicity in PC12 cells. Arch. Pharm. Res. 40, 631–639 (2017). https://doi.org/10.1007/s12272-017-0908-z

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