title: Gastrodin inhibits glutamate-induced apoptosis of PC12 cells via inhibition of CaMKII/ASK-1/p38 MAPK/p53 signaling cascade.
abstract: Previous research demonstrated that glutamate induces neuronal injury partially by increasing intracellular Ca(2+) concentrations ([Ca(2+)]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 [Ca(2+)]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.
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 230038, China.
authors.forename: Genling
authors.initials: G
authors.lastname: Jiang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Wu
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Qinling
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001592:Benzyl Alcohols / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001592:Benzyl Alcohols; D005960:Glucosides; D016159:Tumor Suppressor Protein p53; D018698:Glutamic Acid; C045345:gastrodin; D045304:Cytochromes c; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5