title: MADP, a salidroside analog, protects hippocampal neurons from glutamate induced apoptosis.
abstract: OBJECTIVE
  To investigate the anti-apoptotic effect of MADP, an analog of salidroside, against glutamate induced apoptosis in the cultured rat hippocampal neurons.
  
  
  METHODS
  Cytotoxicity was determined by the MTT method and lactate dehydrogenase release to the medium. Cell apoptosis was evaluated by Hoechst 33342 staining, TUNEL assay and flow cytometric analysis. Western blotting was applied for detecting protein levels of cellular signaling molecules.
  
  
  RESULTS
  Our results showed that glutamate exposure significantly induces cell apoptosis, whereas the pretreatment of salidroside or MADP remarkably improves cell viability. Most importantly, the anti-apoptotic effect of MADP against glutamate insult is superior to salidroside. To explore the involved mechanisms, we measured some pro-apoptotic and anti-apoptotic protein levels, and several cell survival signaling pathways were analyzed as well. No visible alterations in Bcl-2 and Bax protein levels were observed by MADP or salidroside. Akt and JNK phosphorylation was robustly stimulated by MADP in the glutamate-treated neurons. Salidroside treatment results in a slight activation in Akt, while no significant alteration in JNK activity was observed.
  
  
  CONCLUSIONS
  MADP exhibits higher capacity to attenuate glutamate induced cell apoptosis in the cultured rat hippocampal neurons, suggesting that MADP might be a better candidate than salidroside for developing novel drugs treating neuron loss associated disorders.
authors.affiliation: Department of Pediatric Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xian
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China.
authors.forename: Meihong
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China.
authors.forename: Bingxin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China. Electronic address: suncheng1975@ntu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China. Electronic address: yangym@ntu.edu.cn.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D005960:Glucosides; D018696:Neuroprotective Agents; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D018698:Glutamic Acid; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C009172:rhodioloside; D000117:Acetylglucosamine
keywords: Apoptosis; Glutamate excitotoxicity; Hippocampal neurons; Neurodegeneration; Salidroside analog