Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/43530
Title: Tanshinone II A, a multiple target neuroprotectant, promotes caveolae-dependent neuronal differentiation
Authors: Zhao, Y
Xu, P
Hu, S
Du, L
Xu, Z
Zhang, H
Cui, W
Mak, S
Xu, D
Shen, J
Han, Y 
Liu, Y
Xue, M
Keywords: BDNF
Caveolin-1
Neurodegeneration
Neuronal differentiation
NGF
Tanshinone II A
Issue Date: 2015
Publisher: Elsevier
Source: European journal of pharmacology, 2015, v. 765, p. 437-446 How to cite?
Journal: European journal of pharmacology 
Abstract: Neuron loss is one fundamental features of neurodegenerative diseases. Stimulating endogenous neurogenesis, especially neuronal differentiation, might potentially provide therapeutic effects to these diseases. In this study, tanshinone II A (TIIA), a multiple target neuroprotectant, was demonstrated to promote dose-dependent neuronal differentiation in three cell models of immortalized C17.2 neuronal stem cells, rat embryonic cortical neural stem cells (NSCs) and rat PC12 pheochromocytoma cells. In particular, TIIA exerted promising effects on NSCs even at the dose of 3 nM. In PC12 cells, TIIA activated mitogen-activated protein kinase 42/44 (MAPK42/44) and its downstream transcription factor, cAMP response element-binding protein (CREB). In addition, TIIA up-regulated the expressions of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The MEK inhibitor and the antagonist to the receptors of NGF and BDNF could partially attenuate the differentiation effects, indicating that MAPK42/44 mediated BDNF and NGF signals were involved in TIIA's differentiation effects. Caveolin-1 (CAV-1), the major functional protein of membrane caveolae, plays critical roles in the endocytosis of exogenous materials. CAV1, which was activated by TIIA, might help TIIA transport across cell membrane to initiate its differentiation effects. It was proven by the evidences that suppressing the function of caveolin inhibited the differentiation effects of TIIA. Therefore, we concluded that TIIA promoted neuronal differentiation partially through MAPK42/44 mediated BDNF and NGF signals in a caveolae-dependent manner.
URI: http://hdl.handle.net/10397/43530
ISSN: 0014-2999
DOI: 10.1016/j.ejphar.2015.09.006
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