Journal Article

Necrostatin-1 protection of dopaminergic neurons

Jing-ru Wu Jie Wang Sheng-kui Zhou Long Yang Jia-le Yin Jun-ping Cao Yan-bo Cheng

2015

Overview

Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson＇s disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before exposure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death process of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range（5–30 μM） elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Parkinson＇s disease.

• Publisher: Medknow Publications and Media Pvt. Ltd,Medknow Publications & Media Pvt. Ltd,Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China%Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China%Department of Neurology, Afifliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China,Medknow Publications & Media Pvt Ltd,Wolters Kluwer Medknow Publications
• Subject: Apoptosis / Autophagy / Bcl-2 / Biotechnology industry / Care and treatment / Disease / Dopamine / Dopaminergic mechanisms / Genetic aspects / Ischemia / Membranes / nerve regeneration; neurodegeneration; necrostatin-1; necroptosis; apoptosis; cytotoxicity; 6-hydroxydopamine; Parkinson′s disease; neuroprotection; autophagy; necrosis; programmed cell death; neurodegenerative disease; PC12 cells; neural regeneration / Oxidative stress / Parkinson disease / Parkinson's disease / PC12细胞 / Physiological aspects / Proteins / Signal transduction / 多巴胺能神经元 / 死亡过程 / 神经保护 / 线粒体膜电位 / 组织蛋白酶B / 细胞凋亡