title: Schizandrin protects primary rat cortical cell cultures from glutamate-induced apoptosis by inhibiting activation of the MAPK family and the mitochondria dependent pathway.
abstract: Glutamate-induced excitotoxicity has been implicated in a variety of neuronal degenerative disorders. In the present study, we investigated the possible neuroprotective effects of schizandrin against apoptosis of primary cultured rat cortical cells induced by glutamate. Glutamate (10 μM) administered for 24 h decreased the expression of Bcl-2 and Bcl-X(L) protein, whereas increased the expression of Bax, Bak, apoptosis inducing factor (AIF), endonuclease G (Nodo G) and endoplasmic reticulum (ER) stress of caspase-12. Pretreatment with schizandrin (100 μM) before glutamate treatment increased the Bcl-X(L) and Bcl-2 expression and decreased Bax, Bak, AIF, Nodo G and caspase-12 compared with those only treated with glutamate. Furthermore, glutamate-induced phosphorylation of JNK, p38 and ERK mitogen-activated protein kinases (MAPK), and these effects were attenuated by schizandrin (100 μM) treatment. These results suggest that schizandrin possesses the neuroprotective effects. The molecular mechanisms of schizandrin against glutamate-induced apoptosis may involve the regulation of Bcl-2 family proteins expression, and ER stress through blocking the activation of JNK, ERK and p38 MAPK.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 402, Taiwan.
authors.forename: Meng-Shiou
authors.initials: MS
authors.lastname: Lee
authors.forename: Jung
authors.initials: J
authors.lastname: Chao
authors.forename: Jiin-Cherng
authors.initials: JC
authors.lastname: Yen
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lin
authors.forename: Fan-Shiu
authors.initials: FS
authors.lastname: Tsai
authors.forename: Ming-Tsuen
authors.initials: MT
authors.lastname: Hsieh
authors.forename: Wen-Huang
authors.initials: WH
authors.lastname: Peng
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000009:adverse effects*; D017705:Lignans / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000494:pharmacology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C494774:Bak1 protein, rat; C494828:Bax protein, rat; D034242:Cyclooctanes; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D017705:Lignans; D018696:Neuroprotective Agents; D011083:Polycyclic Compounds; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D018698:Glutamic Acid; D020928:Mitogen-Activated Protein Kinases; C506443:Casp12 protein, rat; D053454:Caspase 12; C011105:schizandrin