Abstract
Emodin is a natural anthraquinone derivative with numerous beneficial effects, including antioxidant properties, anti-tumor activities, and protecting the nerves. Zinc-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD) and Parkinson’s disease (PD). Here, the protective activity of emodin inhibiting zinc-induced neurotoxicity and its molecular mechanisms such as cellular Zn2+ influx and zinc-induced gene expression were examined using human neuroblastoma cells (SH-SY5Y cells). Our findings showed that emodin obviously enhanced cell viability and reduced cell apoptosis and lactate dehydrogenase release. Bedsides, we detected a decrease of intracellular Zn2+ concentration after SH-SY5Y cells were pretreated with emodin. Simultaneously, the expression of zinc transporter-1, metallothionein-1, and metallothionein-2 were weakened in emodin-pretreated SH-SY5Y cells. In addition, emodin prevented the depletion of NAD+ and ATP induced by zinc. Emodin also reduced intracellular reactive oxygen species and endoplasmic reticulum-stress levels. Strikingly, emodin elevated SH-SY5Y cell viability and inhibited cell apoptosis caused by AMP-activated protein kinase signaling pathway activation. Thus, emodin could protect against neurotoxicity induced by Zn2+ in neuroblastoma SH-SY5Y cells. It is expected to have future therapeutic potential for VD or PD and other neurodegenerative diseases.
Highlights
The incidence of senile dementia is increasing in a rapidly aging world
The role and mechanism of emodin in zinc-induced neurotoxicity have not been elucidated. This investigation shows that emodin reduces apoptosis induced by excessive Zn2+ in human neuroblastoma SH-SY5Y cells with elevation of cellular ATP
Zn2+ transport into or out of neurons has been reported to be regulated by various molecules including calcium-permeable AMPA/Kainate channels [30], transient receptor potential channels (TRP channels) [31], Na+/Zn2+ exchanger [32], and zinc transporters [18]
Summary
The incidence of senile dementia is increasing in a rapidly aging world. Approximately 65.7 million people will be living with senile dementia by 2030 [1]. It is urgently to study the potential pathogenesis of VD or PD and to find drugs to prevent or treat senile dementia. Studies found that the excessive entry of zinc (Zn2+) into neurons is critical to ischemia-induced neuronal death and, eventually, contributes to the pathogenesis of VD and PD [2,3,4]. Kim and co-workers [5] indicated that elevation of intracellular Zn2+ level induced various functional abnormalities of neurons, leading to the toxicity and death of neurons. ATP depletion and ROS production in neuron cells characterize zinc-induced neurotoxicity. The role and mechanism of emodin in zinc-induced neurotoxicity have not been clarified. The present study is aimed to investigate the potential protective activity of emodin on zinc-induced neurotoxicity. The potential molecular mechanisms were explored in SHSY5Y neuroblastoma cells, providing clues for novel VD and PD treatments
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