Genistein protects against Aß25-35 induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers.

BACKGROUND: Deposition of aggregated amyloid beta (Aß) 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 Aß25-35 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 Aß25-35 induced apoptosis of neurons. RESULTS: We found that Gen dramatically suppressed the activation by Aß25-35 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 Aß25-35 induced PC12 cell cytotoxicity. CONCLUSION: Taken together, the results suggested that Gen protects PC12 cells from Aß25-35 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 Aß25-35 toxicity, and the neuroprotective action of Gen.

Environmental regulations, green development of agriculture, and residents' health-empirical analysis of Yangtze River Economic Belt in China.

Environmental pollution and food safety have become key public health issues to be addressed in China. Since they are closely related to the green development of agriculture, it is of great practical significance to elucidate the intrinsic relationships between green development of agriculture, environmental regulation and residents' health. Based on the panel data of the Yangtze River Economic Belt from 2011 to 2020, this study investigates the impacts of environmental regulation and green development of agriculture on residents' health and the influencing mechanism by applying fixed effects method, mediating effectsmethod and the spatial Dubin method. Results show that the use of chemical fertilizers, pesticides and agricultural films is harmful to residents' health; environmental regulation has a negative correlation with the green development of agriculture and affect residents' health through mediating effects; the green development of agriculture has negative spillover effects on residents' health, indicating that purchasing finished products instead of producing locally reduces the input of production factors such as chemical fertilizers and pesticides and transfers health risks associated with agricultural production activities to neighboring areas. Intensifying command-and-control environmental regulation will induce the expansion of hidden economic activities and harm local residents' health, while intensifying market-incentive environmental regulation will lead to the 'Pollution Haven' phenomenon because of the 'race to the bottom', in government and is harmful to the health of residents in neighboring areas. Therefore, it is necessary to formulate reasonable and feasible policies and strengthen the control and prevention of agricultural pollution to enhance green development of agriculture and improve residents' health.

The effect of geniste on Aß25-35-induced PC12 cell apoptosis through the JNK-dependent Fas pathway.

The ß-amyloid protein (Aß) is considered to be the key factor for inducing Alzheimer's disease (AD). In recent years, the neuroprotective effects of genistein have drawn increasing attention. However, the molecular mechanisms of GEN (genistein) against Aß are unclear. In the present study, we investigated the inhibitory effects of GEN on Aß25-35-induced apoptosis in cultured PC12 cells and the related signaling pathway. Our data show that GEN significantly inhibited Aß25-35-induced apoptosis of PC12 cells. GEN suppressed Aß25-35-induced JNK activation and the JNK-dependent upregulation of Fas/FasL at the mRNA and protein levels induced by Aß25-35 were significantly decreased by GEN. Additionally, GEN inhibited mRNA expression and activity of caspase-3 and caspase-8 induced by Aß25-35. Together, these findings showed that Aß-induced apoptosis of PC12 cells proceeds through the Fas/FasL pathway. The JNK signaling plays a critical role in regulating the anti-apoptotic effects of genistein. Thus, our results suggest that genistein can inhibit Aß-induced apoptosis of PC12 cells through blockage of the JNK activation and subsequent suppression of the JNK-dependent Fas/FasL pathway.