title: Pterostilbene mediates neuroprotection against oxidative toxicity via oestrogen receptor α signalling pathways.
abstract: OBJECTIVE
  Accumulating evidence indicated protective role of phytoestrogens against neuronal damage induced by various insults, such as amyloid beta, oxygen deprivation and mitochondrial toxins. Hydrogen peroxide (H2 O2 ) influences the mitochondrial membrane potential, which eventually results in cell apoptosis. In this study, we investigated the effects and possible mechanisms of a phytoestrogen, pterostilbene (PTER), in cell apoptosis induced by H2 O2 in human neuronal SH-SY5Y cells. We also analysed the involvement of oestrogen receptors, oestrogen receptor-α and -β (ER-α and ER-β) in the protective role of PTER.
  
  
  METHODS
  The effects of PTER on H2 O2 -stimulated cell were examined using MTT and FACS analysis. The signal pathways and estrogen receptors involved in PTER's effects were investigated using MTT and Western blot analysis.
  
  
  RESULTS
  The results showed that H2 O2 treatment significantly reduced cell viability in SY5Y cells, which was protected by PTER treatment. We also found that H2O2 inhibited the PI3K/AKT and MAPK/ERK signalling pathways, whereas PTER treatment restored these signalling pathways. We also found that the PTER effect could be largely blocked by an ER-α antagonist, 3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP), but not by an ER-β antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a] pyrimidin-3-yl]phenol (PHTPP), suggesting that ER-α is a major player in the neuroprotective activity of PTER.
  
  
  CONCLUSIONS
  Our study thus demonstrates that PTER is an effective neuroprotective agent presumably through ER-α-mediated signalling pathways.
authors: Department of Genetics, Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan, Shandong, China.
authors: Zhen
authors: Z
authors: Song
authors: Shuai
authors: S
authors: Han
authors: Xiaohua
authors: X
authors: Pan
authors: Yaoqin
authors: Y
authors: Gong
authors: Molin
authors: M
authors: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C524478:1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole; C556295:4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D013267:Stilbenes; C107773:pterostilbene; D006861:Hydrogen Peroxide
keywords: neuroprotection; oestrogen receptor; phytoestrogen; pterostilbene