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

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(25–35) 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(25–35) induced apoptosis of neurons. RESULTS: We found that Gen dramatically suppressed the activation by Aβ(25–35) 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(25–35) induced PC12 cell cytotoxicity. CONCLUSION: Taken together, the results suggested that Gen protects PC12 cells from Aβ(25–35) 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(25–35) toxicity, and the neuroprotective action of Gen. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-016-0329-9) contains supplementary material, which is available to authorized users.