title: Genistein protects against Aβ25-35induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers.
abstract: Deposition of aggregated amyloid beta (Aβ) protein is hallmark of Alzheimer's disease, leading to dysfunction and apoptosis of neurons. The isoflavone phytoestrogen compound genistein (Gen) exerts a significant protective effect against Aβ25-35induced neurotoxicity and mitochondrial damage in rat pheochromocytoma (PC12) cells. However, the mechanisms underlying Gen's rescue remain elusive. Therefore we endeavored to research further the molecular mechanisms underlying Gen's inhibition of Aβ25-35induced apoptosis of neurons.
  
  
  
  We found that Gen dramatically suppressed the activation by Aβ25-35of p-c-Jun N-terminal kinase (p-JNK), and also inhibited the JNK-dependent decreased of Bcl-w and increased of Bim. Furthermore, Gen significantly reduced the cytoplasmic concentrations of cytochrome c and Smac protein as well as caspase-3 activity. Additionally, pretreatment with JNK inhibitor SP600125 effectively suppressed Aβ25-35induced PC12 cell cytotoxicity.
  
  
  
  Taken together, the results suggested that Gen protects PC12 cells from Aβ25-35induced neurotoxicity by interfering with p-JNK activation, thus attenuating the JNK-dependent apoptosis through the mitochondrial pathway. These findings constitute novel insights into the pathway for Aβ25-35toxicity, and the neuroprotective action of Gen.
authors.affiliation: Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.
authors.forename: Fuling
authors.initials: F
authors.lastname: You
authors.affiliation: Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.
authors.forename: Yaojie
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.
authors.forename: Jingrong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China. yanghong2329@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D019833:Genistein / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; C491072:Bcl2l2 protein, rat; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C074636:amyloid beta-protein (25-35); D045304:Cytochromes c; D019833:Genistein; D048031:JNK Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Alzheimer’s disease; Apoptosis; Aβ25–35; Bcl-2; Genistein; JNK