Genistein Protects Against Aβ Induced Apoptosis of PC12 Cells Through JNK Signaling and Modulation of Bcl-2 Family Messengers

Overview

Journal BMC Neurosci

Publisher Biomed Central

Specialty Neurology

Date 2017 Jan 14

PMID 28081713

Citations 9

Authors

Fuling You

Qiao Li

Guifang Jin

Yaojie Zheng

Jingrong Chen

Hong Yang

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

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