Cellular and Molecular Neurobiology

, Volume 34, Issue 4, pp 591–602 | Cite as

Gastrodin Inhibits Glutamate-Induced Apoptosis of PC12 Cells via Inhibition of CaMKII/ASK-1/p38 MAPK/p53 Signaling Cascade

  • Genling Jiang
  • Haiyun Wu
  • Yuqin Hu
  • Jun Li
  • Qinling Li
Original Research


Previous research demonstrated that glutamate induces neuronal injury partially by increasing intracellular Ca2+ concentrations ([Ca2+]i), and inducing oxidative stress, leading to a neurodegenerative disorder. However, the mechanism of glutamate-induced injury remains elusive. Gastrodin, a major active component of the traditional herbal agent Gastrodia elata (GE) Blume, has been recognized as a potential neuroprotective drug. In the current study, a classical injury model based on glutamate-induced cell death of rat pheochromocytoma (PC12) cells was used to investigate the neuroprotective effect of gastrodin, and its potential mechanisms involved. In this paper, the presence of gastrodin inhibits glutamate-induced oxidative stress as measured by the formation of reactive oxygen species (ROS), the level of malondialdehyde (MDA), mitochondrial membrane potential (MMP), and superoxide dismutase (SOD); gastrodin also prevents glutamate-induced [Ca2+]i influx, blocks the activation of the calmodulin-dependent kinase II (CaMKII) and the apoptosis signaling-regulating kinase-1 (ASK-1), inhibits phosphorylation of p38 mitogen-activated kinase (MAPK). Additionally, gastrodin blocked the expression of p53 phosphorylation, caspase-3 and cytochrome C, reduced bax/bcl-2 ratio induced by glutamate in PC12 cells. All these findings indicate that gastrodin protects PC12 cells from the apoptosis induced by glutamate through a new mechanism of the CaMKII/ASK-1/p38 MAPK/p53-signaling pathway.


Gastrodin Glutamate Apoptosis Calmodulin-dependent kinase II (CaMKII) Apoptosis signaling-regulating kinase-1 (ASK-1) 


Conflict of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Genling Jiang
    • 1
  • Haiyun Wu
    • 1
  • Yuqin Hu
    • 2
  • Jun Li
    • 1
  • Qinling Li
    • 1
    • 3
  1. 1.Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese MedicineAnhui University of Chinese MedicineHefeiChina
  2. 2.Department of Clinical CollegeAnhui Medical UniversityHefeiChina
  3. 3.Anqing Medical and Pharmaceutical CollegeAnqingChina

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