Genistein protects against Aβ 25-35 induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers

• Published in: BMC neuroscience Vol. 18; no. 1; p. 12
• Main Authors: You, Fuling, Li, Qiao, Jin, Guifang, Zheng, Yaojie, Chen, Jingrong, Yang, Hong
• Format: Journal Article
• Language: English
• Published: England 12.01.2017
• Subjects: Amyloid beta-Peptides - toxicity; Animals; Apoptosis - drug effects; Apoptosis - physiology; Bcl-2-Like Protein 11 - metabolism; Carrier Proteins - metabolism; Caspase 3 - metabolism; Cell Survival - drug effects; Cell Survival - physiology; Cytochromes c - metabolism; Drug Evaluation, Preclinical; Genistein - pharmacology; JNK Mitogen-Activated Protein Kinases - metabolism; Mitochondrial Proteins - metabolism; Neurons - drug effects; Neurons - pathology; Neurons - physiology; Neuroprotective Agents - pharmacology; PC12 Cells; Peptide Fragments - toxicity; Polymerase Chain Reaction; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; RNA, Messenger - metabolism; Signal Transduction - drug effects; Bcl-2; Alzheimer’s disease; Genistein; JNK; Apoptosis; Aβ25–35
• ISSN: 1471-2202

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 Aβ induced 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 Aβ induced apoptosis of neurons. We found that Gen dramatically suppressed the activation by Aβ of 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 Aβ induced PC12 cell cytotoxicity. Taken together, the results suggested that Gen protects PC12 cells from Aβ induced 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 Aβ toxicity, and the neuroprotective action of Gen.