Tanshinone II A, a multiple target neuroprotectant, promotes caveolae-dependent neuronal differentiation

Yuming Zhao, Pingxiang Xu, Shengquan Hu, Libo Du, Zhiqing Xu, Huan Zhang, Wei Cui, Shinghung Mak, Daping Xu, Jianggang Shen, Yifan Han, Yang Liu, Ming Xue

Research output: Journal article publicationJournal articleAcademic researchpeer-review

16 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)437-446
Number of pages10
JournalEuropean Journal of Pharmacology
Volume765
DOIs
Publication statusPublished - 15 Oct 2015

Keywords

  • BDNF
  • Caveolin-1
  • Neurodegeneration
  • Neuronal differentiation
  • NGF
  • Tanshinone II A

ASJC Scopus subject areas

  • Pharmacology

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